Affinage

LIN28B

Protein lin-28 homolog B · UniProt Q6ZN17

Length
250 aa
Mass
27.1 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LIN28B is a post-transcriptional regulator that governs developmental timing, stem-cell identity, and oncogenesis through both let-7-dependent and let-7-independent mechanisms (PMID:22118463, PMID:24142874). Distinct from LIN28A, LIN28B acts in the nucleus, where it sequesters primary let-7 transcripts and blocks their processing by the Microprocessor, thereby de-repressing let-7 target oncogenes including MYCN and HMGA2 (PMID:22118463, PMID:23042116, PMID:32634132). This let-7 blockade underlies LIN28B's capacity to induce neuroblastoma in the sympathetic adrenergic lineage via elevated MYCN (PMID:23042116) and to drive neuroendocrine prostate cancer through an HMGA2→SOX2 cascade (PMID:32634132). Independently of let-7, LIN28B directly binds large numbers of mRNAs, using its cold-shock and zinc-finger RNA-binding domains, to stabilize transcripts and augment their translation (PMID:24142874, PMID:23770886); it also engages ribosomes and ribosomal-complex transcripts to boost translational output (PMID:31959994, PMID:34779407). Through these direct RNA interactions LIN28B suppresses BCL11A translation to induce fetal hemoglobin during human erythropoiesis (PMID:31959994, PMID:23798711) and, together with the let-7→Arid3a and let-7→Cbx2 axes, controls the fetal-to-adult hematopoietic switch and fetal B-1 lymphopoiesis (PMID:25753579, PMID:35385744). In a separate nuclear role, LIN28B binds active gene promoters via protein-protein interaction with the transcription factor ZNF143 to activate adrenergic core regulatory transcription, a function retained by a let-7-incapable mutant (PMID:32601179). LIN28B activity is tightly controlled: its subcellular distribution is set by PKCβ-mediated Ser243 phosphorylation driving nuclear entry (PMID:33107691) and by Merlin/NF2 dephosphorylation that sequesters it in the cytoplasm (PMID:26997273); its protein level is stabilized at G1/S by the deubiquitylase OTUD6B to drive MYC and S-phase entry (PMID:36059274) and antagonized by the E3 ligase TRIM71 (PMID:27821801); and its transcription is gated epigenetically by SIRT6 and induced by NF-κB, TCF7L2, and MYCN (PMID:27180906, PMID:25368430, PMID:25744721, PMID:26123663).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2006 Medium

    Established the basic cellular behavior of LIN28B before its molecular function was known, showing it is largely cytoplasmic with cell-cycle-dependent nuclear shuttling and that it promotes proliferation.

    Evidence Subcellular localization and tet-off inducible expression in Huh7 cells

    PMID:16971064

    Open questions at the time
    • No RNA target or molecular mechanism defined
    • Trigger for nuclear translocation not identified
  2. 2011 High

    Resolved how LIN28B differs mechanistically from LIN28A, showing it represses let-7 in the nucleus by sequestering pri-let-7 from the Microprocessor rather than via Zcchc11/TUTase.

    Evidence Zcchc11 depletion, nuclear fractionation, and Lin28A/B comparison in human cancer cells

    PMID:22118463

    Open questions at the time
    • Structural basis of pri-let-7 sequestration not resolved
    • How nuclear localization is regulated unknown
  3. 2011 Medium

    Provided first evidence of a let-7-independent function by showing LIN28B directly binds and upregulates specific mRNAs (LGR5, PROM1) while also driving transformation.

    Evidence RIP, let-7 restoration, and migration/invasion assays in colon cancer cells

    PMID:21625210

    Open questions at the time
    • Binding shown by RIP without nucleotide resolution
    • Translational vs stability contribution not separated
  4. 2012 High

    Demonstrated LIN28B is oncogenic in vivo through the let-7→MYCN axis, establishing causal sufficiency for neuroblastoma initiation.

    Evidence Transgenic LIN28B expression in sympathetic adrenergic lineage with let-7 and MYCN readouts

    PMID:23042116

    Open questions at the time
    • Relative contribution of let-7-independent functions in this model not dissected
  5. 2013 High

    Defined the genome-wide direct RNA-binding landscape of LIN28B at nucleotide resolution and linked binding to enhanced translation, anchoring its let-7-independent role in transcriptome-wide mRNA regulation.

    Evidence CLIP-seq/PAR-CLIP with proteomics and in vivo intestinal transgenic/let-7 rescue mouse models

    PMID:23770886 PMID:24142874

    Open questions at the time
    • Functional significance varies by tissue — let-7 effect supersedes direct binding in intestine
    • Domain contributions to individual targets not fully resolved
  6. 2013 High

    Connected LIN28B to fetal hemoglobin regulation, placing the LIN28B→let-7→BCL11A axis upstream of γ-globin.

    Evidence Lentiviral LIN28B knockdown/overexpression and let-7 suppression in adult human erythroblasts

    PMID:23798711

    Open questions at the time
    • At this stage BCL11A regulation attributed to let-7, not direct translational control
  7. 2015 Medium

    Identified multiple transcriptional and post-transcriptional inputs controlling LIN28B abundance and localization, framing it as a tightly gated node in cancer and contact-dependent signaling.

    Evidence ChIP for NF-κB p65 and TCF7L2 at LIN28B intron 1, MYCN ChIP/miR-26a-5p assays, and Merlin/NF2 Co-IP with fractionation

    PMID:25368430 PMID:25744721 PMID:26123663 PMID:26997273

    Open questions at the time
    • Each regulatory circuit shown in a single lab/context
    • Interplay among the competing inputs unresolved
  8. 2015 Medium

    Extended LIN28B/let-7 control to fetal-specific immune and developmental programs, identifying Arid3a, TGF-β signaling components, and cochlear timing as effectors.

    Evidence Transgenic/knockdown Lin28b with let-7 modulation in fetal B-1 cells, fetal Tregs, and conditional cochlear mouse models

    PMID:25753579 PMID:26139524 PMID:27793996

    Open questions at the time
    • Direct vs indirect contributions to each lineage program not fully separated
  9. 2015 Medium

    Expanded the oncogenic effector network of LIN28B by showing convergence on RAN/RANBP2 and AURKA in neuroblastoma.

    Evidence RIP for LIN28B-RAN mRNA binding, RANBP2/AURKA activity, and 12q24 gain analysis

    PMID:26481147

    Open questions at the time
    • Mechanism of AURKA activation downstream of RAN not fully detailed
  10. 2018 Medium

    Catalogued multiple direct mRNA targets through which LIN28B drives cancer phenotypes, establishing recurrent stability/translation control of growth and invasion mediators.

    Evidence RIP for AKT2, CLDN1, and NRP-1 mRNAs with downstream FOXO3A/BIM, NOTCH3, and Wnt/β-catenin readouts across cancer models

    PMID:29787985 PMID:30174831 PMID:37318881

    Open questions at the time
    • Each target validated in a single cancer context
    • Common sequence/structural binding determinants across targets not unified
  11. 2019 High

    Showed LIN28B cooperates with a partner RNA-binding protein, Igf2bp3, co-binding shared mRNA sites to reactivate fetal-like programs more efficiently than either factor alone.

    Evidence Proteomics, RIP co-binding mapping, scRNA-seq, and enforced co-expression in adult HSPCs

    PMID:31221665

    Open questions at the time
    • Stoichiometry and structural basis of co-binding unresolved
  12. 2020 High

    Defined a let-7-independent translational mechanism for BCL11A and a domain-resolved role in ribosomal-transcript translation, mechanistically separating LIN28B's direct RNA functions from let-7 repression.

    Evidence Ribosome association/RIP for BCL11A and polyribosome profiling with CSD/ZNF domain mutagenesis in erythroid and neuroblastoma systems

    PMID:31959994 PMID:34779407

    Open questions at the time
    • How LIN28B selects ribosomal vs other transcripts not fully defined
  13. 2020 High

    Revealed a chromatin-associated, let-7-independent nuclear function in which LIN28B partners with ZNF143 to activate transcription at active promoters.

    Evidence ChIP-seq, Co-IP of LIN28B-ZNF143, let-7-processing-deficient mutant, and in vivo neuroblastoma model

    PMID:32601179

    Open questions at the time
    • Whether LIN28B contacts DNA directly or only via ZNF143 not resolved
  14. 2020 Medium

    Identified PKCβ-mediated Ser243 phosphorylation as a direct switch driving LIN28B nuclear translocation downstream of KRAS, with a TET3 feedback loop.

    Evidence PKCβ kinase assay, subcellular fractionation, and let-7i/TET3 feedback validation in pancreatic cancer

    PMID:33107691

    Open questions at the time
    • Single lab; interplay with Merlin/NF2-controlled localization untested
  15. 2020 Medium

    Demonstrated LIN28B-dependent stabilization of disease-defining transcripts in additional tumors, broadening its mRNA-stabilizing oncogenic role.

    Evidence EWS-FLI1 mRNA stability and pharmacological LIN28B inhibition in Ewing sarcoma with in vivo assays

    PMID:32234488

    Open questions at the time
    • Effect restricted to ~10% of cases; direct binding to EWS-FLI1 mRNA not shown at nucleotide resolution
  16. 2021 Medium

    Linked LIN28B to RNA modification recognition, showing it reads m5C-modified GRB2 mRNA to stabilize it and activate growth signaling.

    Evidence Transcriptome-wide m5C profiling, NSUN2 KO, and RIP in esophageal squamous cell carcinoma

    PMID:34345012

    Open questions at the time
    • Direct preference of LIN28B for m5C marks vs sequence not biochemically isolated
  17. 2022 High

    Resolved cell-cycle-specific control of LIN28B protein stability, identifying OTUD6B as a deubiquitylase that stabilizes it at G1/S to drive MYC and S-phase entry.

    Evidence DUB screen, ubiquitylation assays, cell-cycle synchronization, and xenografts in multiple myeloma

    PMID:36059274

    Open questions at the time
    • The opposing E3 ligase in this context not defined
    • Relation to TRIM71-mediated degradation untested
  18. 2022 Medium

    Clarified upstream epigenetic and post-translational control by SIRT6, both repressing the LIN28B promoter and directly deacetylating the protein.

    Evidence ChIP at the Lin28B promoter plus Co-IP/deacetylation assays in pancreatic cancer and vascular endothelial cells

    PMID:27180906 PMID:35978508

    Open questions at the time
    • Functional consequence of LIN28B acetylation site(s) not mapped
  19. 2023 High

    Provided structural insight into the LIN28B locus as a model nucleosome substrate for pioneer-factor OCT4-mediated chromatin opening, and identified ALDH2 as a competitor that blocks LIN28B from its mRNA target ELK3.

    Evidence Cryo-EM of OCT4-LIN28B nucleosome complexes; Co-IP and binding-competition assays for ALDH2-LIN28B in aortic aneurysm models

    PMID:37327775 PMID:37822152

    Open questions at the time
    • OCT4 study addresses LIN28B-locus chromatin, not LIN28B protein function
    • ALDH2 competition shown in single vascular context

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the competing localization, stabilization, and transcription circuits are integrated to set LIN28B activity in a given cell, and how let-7-dependent vs ZNF143/ribosomal let-7-independent functions are partitioned, remains unresolved.
  • No unified model coordinating PKCβ/Merlin localization, OTUD6B/TRIM71 stability, and SIRT6/NF-κB transcription
  • Quantitative apportioning of let-7-dependent vs independent contributions per tissue lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 10 GO:0045182 translation regulator activity 3 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 5 GO:0005829 cytosol 2 GO:0005840 ribosome 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-74160 Gene expression (Transcription) 1
Partners
ALDH2IGF2BP3NF2OTUD6BSIRT6TRIM71ZNF143

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 Unlike Lin28A, Lin28B represses let-7 processing through a Zcchc11-independent mechanism by functioning in the nucleus, where it sequesters primary let-7 transcripts (pri-let-7) and inhibits their processing by the Microprocessor complex. Zcchc11 depletion experiments, nuclear fractionation, functional comparison of Lin28A vs Lin28B mechanisms in human cancer cells Cell High 22118463
2012 LIN28B signals through repression of let-7 miRNAs, which consequently results in elevated MYCN protein expression in neuroblastoma cells, and LIN28B expression in the sympathetic adrenergic lineage is sufficient to induce neuroblastoma development in a mouse model. Mouse transgenic model (LIN28B expression in sympathetic adrenergic lineage), let-7 miRNA measurement, MYCN protein expression analysis, in vivo neuroblastoma induction Nature genetics High 23042116
2006 LIN28B protein is predominantly localized in the cytoplasm but shows cell cycle-dependent nuclear translocation in Huh7 cells, and induced expression of LIN28B promotes cancer cell proliferation. Western blot with anti-LIN28B antibody, subcellular localization studies, tet-off inducible expression system, cell proliferation assay Gene Medium 16971064
2016 SIRT6 loss results in histone hyperacetylation at the Lin28B promoter, Myc recruitment, and pronounced induction of Lin28B; SIRT6 thus suppresses pancreatic cancer through epigenetic control of Lin28b expression. ChIP for histone acetylation and Myc at Lin28B promoter, SIRT6 loss-of-function mouse models, Lin28B knockdown/rescue experiments in PDAC Cell High 27180906
2013 LIN28B directly binds a large number of mRNAs in the human transcriptome and modestly augments protein levels of these target mRNAs in vivo; furthermore, Let-7 miRNAs have a profound repressive effect on intestinal tissue growth that supersedes LIN28B-independent mRNA binding effects. CLIP-seq (ribonucleoprotein cross-linking, immunoprecipitation, high-throughput sequencing), intestine-specific transgenic mouse models, Let-7 deletion (mirLet7c2/mirLet7b genes), intestine-specific Let-7 rescue Genes & development High 24142874
2011 LIN28B promotes colon cancer cell migration, invasion and transformation of immortalized colonic epithelial cells; additionally, LIN28B protein directly binds LGR5 and PROM1 mRNA to increase their expression independently of let-7 repression, suggesting a let-7-independent mechanism of post-transcriptional regulation. Constitutive LIN28B expression in colon cancer cells, RNA immunoprecipitation (RIP) of LGR5 and PROM1 mRNA, let-7 restoration experiments, migration/invasion assays Oncogene Medium 21625210
2013 LIN28B directly binds most expressed mRNAs and let-7 microRNA family members as identified by PAR-CLIP at nucleotide resolution; the position of binding sites reflects the known structural orientation of the CSD and ZNF RNA-binding domains; LIN28B knockdown reduces protein synthesis from its RNA targets. PAR-CLIP and iDo-PAR-CLIP (nucleotide-resolution binding site mapping), quantitative shotgun proteomics of LIN28B-depleted cells, cell proliferation assays RNA biology High 23770886
2020 LIN28B directly interacts with ribosomes and BCL11A mRNA, suppressing BCL11A mRNA translation independently of its role in regulating let-7 microRNAs, thereby controlling fetal hemoglobin (HbF) induction during human hematopoietic development; BCL11A is identified as the major target of LIN28B-mediated HbF induction. Unbiased genomic and proteomic analyses, ribosome association assays, RNA immunoprecipitation, LIN28B knockdown/overexpression in erythroid cells, let-7-independent functional dissection Nature genetics High 31959994
2013 LIN28B overexpression in adult human erythroblasts reduces let-7 expression, significantly increases fetal hemoglobin (HbF) to >30% of total hemoglobin, and down-regulates BCL11A (a repressor of γ-globin); experimental suppression of let-7 independently reduces BCL11A and increases HbF, placing the LIN28B→let-7→BCL11A axis upstream of γ-globin regulation. Lentiviral transduction for LIN28B knockdown/overexpression in human erythroblasts, qRT-PCR for let-7, HbF measurement, BCL11A expression analysis Blood High 23798711
2015 Lin28B promotes fetal B-1 lymphopoiesis through the transcription factor Arid3a, which is a key target of Let-7; modulation of Let-7 in fetal pro-B cells is sufficient to alter fetal B-1 development, and intact BCR signaling is required for B1a B cell generation from Lin28b-transduced bone marrow progenitors. Transgenic Lin28b expression in adult BM progenitors, Let-7 modulation in fetal pro-B cells, BCR signaling manipulation, Arid3a knockdown/overexpression The Journal of experimental medicine High 25753579
2015 LIN28B activates the LIN28B→let-7→HMGA2 axis in NSCLC via NF-κB p65, which occupies the LIN28B first intron and activates LIN28B transcription; MUC1-C induces this axis as an upstream regulator. ChIP assay demonstrating NF-κB p65 chromatin occupancy at LIN28B intron 1, dominant-negative MUC1-C mutant, peptide inhibitor, siRNA knockdown, HMGA2 expression analysis Molecular cancer research : MCR Medium 25368430
2015 LIN28B promotes fetal regulatory T cell (Treg) differentiation by maintaining expression of TGF-β signaling mediators (TGF-βRI, TGF-βRIII, SMAD2) that are let-7 targets; knockdown of Lin28b in fetal T cells reduces let-7 targets TGF-βRI, TGF-βRIII, and SMAD2, decreasing TGF-β signaling and Treg differentiation. Lin28b knockdown in naive fetal T cells, TGF-β receptor and SMAD2 expression analysis, SMAD2/SMAD3 phosphorylation measurement, in vitro Treg differentiation assay Journal of immunology Medium 27793996
2015 At low cell density, Merlin/NF2 is phosphorylated and does not bind to Lin28B, allowing Lin28B to enter the nucleus and bind to pri-let-7 miRNAs to inhibit their maturation; cell-cell contact triggers Merlin/NF2 dephosphorylation, which sequesters Lin28B in the cytoplasm and permits pri-let-7 maturation, representing a Hippo-independent tumor-suppressive pathway. Merlin/NF2 phosphorylation status analysis, co-immunoprecipitation of Merlin/NF2 and Lin28B, subcellular fractionation, pri-let-7 maturation assays, YAP1/TAZ-independent functional studies Cell reports Medium 26997273
2015 IKKβ sustains cancer cell stemness through a positive feedback loop in which TCF7L2 (TCF4) binds directly to intron 1 of the LIN28B gene to enhance LIN28B expression, and LIN28B in turn promotes TCF7L2 mRNA translation. TCF7L2 ChIP at LIN28B intron 1, LIN28B RNAi, IKKβ pharmacological inhibition, in vivo xenograft models Cancer research Medium 25744721
2015 MYCN regulates LIN28B expression in neuroblastoma via two parallel mechanisms: (1) indirectly via MYCN suppression of miR-26a-5p (which targets LIN28B 3'UTR), establishing an MYCN-miR-26a-5p-LIN28B axis; and (2) directly via MYCN binding to the LIN28B promoter. LIN28B 3'UTR luciferase reporter screen, miR-26a-5p functional assays, ChIP for MYCN at LIN28B promoter, Tet-regulatable MYCN transgene expression system Cancer letters Medium 26123663
2020 LIN28B binds active gene promoters in neuroblastoma cells through protein-protein interaction with the zinc-finger transcription factor ZNF143, activating transcriptional targets including adrenergic core regulatory circuitry transcription factors and GSK3B and L1CAM; a LIN28B mutant unable to inhibit let-7 retains this transcriptional function, defining a let-7-independent nuclear role. ChIP-seq (genome-wide chromatin immunoprecipitation sequencing), co-immunoprecipitation of LIN28B and ZNF143, let-7-processing-deficient LIN28B mutant, in vivo neuroblastoma mouse model Proceedings of the National Academy of Sciences of the United States of America High 32601179
2015 LIN28B identifies RAN as a downstream target by directly binding RAN mRNA and by promoting RAN Binding Protein 2 (RANBP2) expression; LIN28B and RAN signaling converge on Aurora kinase A (AURKA) activity to drive neuroblastoma oncogenesis. LIN28B-RAN mRNA binding assay (RNA immunoprecipitation), RANBP2 expression analysis, AURKA activity measurement, somatic chromosome 12q24 gain analysis Cancer cell Medium 26481147
2019 Lin28b directly interacts with Igf2bp3 (another RNA-binding protein); co-expression of Lin28b and Igf2bp3 in adult HSPCs jointly stabilizes thousands of mRNAs by binding at the same sites, including Pax5 and Arid3a mRNAs, and Igf2bp3 mRNA itself (autoregulatory loop), reactivating fetal-like B-cell development more efficiently than either factor alone. Single-cell RNA sequencing, proteomics (in situ analysis), RNA immunoprecipitation demonstrating co-binding at same mRNA sites, enforced co-expression in adult HSPCs, in vivo B-cell development assay Genes & development High 31221665
2020 LIN28B promotes neuroendocrine prostate cancer (t-NEPC) development through suppression of let-7 miRNA, leading to de-repression of HMGA2, which then drives SOX2 expression; LIN28B depletion by CRISPR inhibited t-NEPC tumorigenesis and xenograft growth. CRISPR-based LIN28B depletion, immunohistochemistry validation in patient biopsies, let-7 and HMGA2 expression analysis, SOX2 expression assay, xenograft tumor model The Journal of clinical investigation High 32634132
2021 NSUN2 induces m5C modification of GRB2 mRNA, and LIN28B acts as a mediator that recognizes m5C-modified GRB2 mRNA to stabilize it, thereby activating PI3K/AKT and ERK/MAPK signaling in esophageal squamous cell carcinoma. Transcriptome-wide m5C profiling, NSUN2 knockout mouse models, RIP demonstrating LIN28B binding to m5C-modified GRB2 mRNA, PI3K/AKT and ERK/MAPK pathway activity measurement Oncogene Medium 34345012
2020 LIN28B regulates the stability of EWS-FLI1 mRNA in a subset (~10%) of Ewing sarcomas; LIN28B depletion leads to decreased EWS-FLI1 expression and its direct transcriptional network, abrogating Ewing sarcoma cell self-renewal and tumorigenicity. LIN28B depletion experiments, EWS-FLI1 mRNA stability assay, pharmacological LIN28B inhibition, in vitro and in vivo tumorigenicity assays Cell reports Medium 32234488
2018 LIN28B directly binds to AKT2 mRNA via RNA-IP and enhances AKT2 protein expression, thereby regulating FOXO3A phosphorylation and decreasing BIM transcription to inhibit apoptosis in ovarian cancer cells. RNA-IP microarray analysis, RNA immunoprecipitation confirming LIN28B-AKT2 mRNA binding, BIM expression analysis, FOXO3A phosphorylation assay, functional apoptosis assay Signal transduction and targeted therapy Medium 30174831
2020 LIN28B alters ribosomal dynamics: it utilizes both its cold shock domain and zinc finger RNA-binding domains to preferentially interact with MYCN-induced transcripts of the ribosomal complex, enhancing their translation in a let-7-independent manner. Polyribosome fractionation with RNA-seq, domain-specific mutagenesis (CSD and ZNF domains), MYCN-amplified neuroblastoma xenografts with in vitro and in vivo metastasis assays The Journal of clinical investigation High 34779407
2020 KRAS promotes Lin28B nuclear translocation through PKCβ, which directly phosphorylates Lin28B at serine 243; nuclear Lin28B then upregulates TET3 mRNA/protein by blocking mature let-7i production, and TET3 further promotes Lin28B expression, forming a Lin28B/let-7i/TET3 feedback loop in pancreatic cancer. PKCβ kinase assay showing S243 phosphorylation of Lin28B, subcellular fractionation demonstrating nuclear translocation, let-7i maturation assays, TET3 expression analysis, feedback loop validation Molecular oncology Medium 33107691
2018 Lin28B regulates the abundance of STAU1 mRNA via regulation of miR-142-3p maturation; as Lin28B decreases during neuronal differentiation, increased mature miR-142-3p reduces STAU1 mRNA stability, establishing a Lin28B→miR-142-3p→STAU1 regulatory axis in neuronal differentiation. Lin28B and STAU1 loss/gain-of-function experiments, miRNA maturation assays, mRNA stability assays for STAU1, transcriptome analysis of SMD targets, mouse neural precursor cell validation Cell death and differentiation Medium 29099484
2022 OTUD6B deubiquitylase directly stabilizes LIN28B protein in a cell cycle-specific manner (at G1/S); stabilized LIN28B drives MYC expression at G1/S to allow rapid S-phase entry in multiple myeloma; silencing OTUD6B or LIN28B inhibits multiple myeloma outgrowth in vivo. DUB screen in multiple myeloma, ubiquitylation assays demonstrating OTUD6B-mediated LIN28B stabilization, cell cycle synchronization, LIN28B knockdown, in vivo xenograft models The EMBO journal High 36059274
2022 SIRT6 directly interacts with and deacetylates Lin28B in vascular endothelial cells; Sirt6 overexpression decreases Lin28B expression and suppresses pyroptosis through the Lin28B/let-7 pathway. Co-immunoprecipitation demonstrating Sirt6-Lin28B interaction, deacetylation assay, Lin28B knockdown experiments, pyroptosis assays (PI staining, GSDMD cleavage, LDH/IL-1β release), let-7 expression measurement International immunopharmacology Medium 35978508
2023 OCT4 targets the LIN28B nucleosome through three OCT4 binding events: two use POUS domains and one uses POUS-loop-POUHD region where POUHD acts as a wedge to unwrap ~25 base pairs of DNA; multiple OCT4 molecules cooperatively open H1-condensed nucleosome arrays containing the LIN28B nucleosome. Cryo-EM high-resolution structural determination of LIN28B nucleosome-OCT4 complexes, ESRRB-nucleosome-OCT4 structural analysis, biochemical nucleosome opening assays Molecular cell High 37327775
2019 Lin28B promotes fetal-like platelet function by acting as a negative regulator of P-selectin expression in megakaryocytes/platelets; LIN28B overexpression in adult mice significantly reduces P-selectin expression in platelets. LIN28B overexpression in adult mice, platelet P-selectin expression measurement, fetal hematopoietic progenitor transplantation experiments, transcriptional analysis of Lin28b and Hmga2 in fetal vs adult megakaryocytes Blood advances Medium 30622145
2015 LIN28B regulates developmental timing in the murine cochlea: prolonged LIN28B expression delays prosensory cell cycle withdrawal and differentiation, causing hair cell and supporting cell patterning defects; LIN28B also positively regulates postnatal hair cell production via let-7-independent mechanisms for differentiation timing. Conditional Lin28B transgenic mouse models, let-7g overexpression transgenic mice, cochlear cell cycle exit and differentiation analysis, Notch inhibition-based HC production assays Proceedings of the National Academy of Sciences of the United States of America Medium 26139524
2020 LIN28B loss of function (conditional deletion or let-7g overexpression) suppresses Akt-mTORC1 activity in cochlear supporting cells, impairing their ability to generate hair cells; LIN28B overexpression increases Akt-mTORC1 activity and allows de-differentiation of maturing supporting cells into progenitor-like cells, and this effect is abolished by mTORC1 inhibitor rapamycin. Conditional LIN28B deletion, let-7g overexpression, murine cochlear organoid and explant cultures, Akt-mTORC1 activity measurement, rapamycin treatment (mTORC1 inhibitor), hair cell counting Proceedings of the National Academy of Sciences of the United States of America High 32826333
2018 LIN28B directly binds to and posttranscriptionally regulates CLDN1 (claudin 1) mRNA in colorectal cancer cells, and LIN28B-mediated CLDN1 expression enhances collective invasion, cell migration, and metastatic liver tumor formation; NOTCH3 is a downstream effector of the LIN28B/CLDN1 axis. RNA immunoprecipitation demonstrating LIN28B-CLDN1 mRNA direct binding, LIN28B KD/OE functional assays, murine metastatic CRC model, bulk RNA sequencing of metastatic tumors, NOTCH3 genetic and pharmacologic manipulation JCI insight Medium 37318881
2018 LIN28B directly binds NRP-1 3'UTR mRNA, increasing NRP-1 mRNA stability and expression, and activates downstream Wnt/β-catenin signaling to confer stemness in gastric cancer cells; NRP-1 knockdown or Wnt/β-catenin antagonism rescues LIN28B overexpression effects. RNA immunoprecipitation demonstrating LIN28B-NRP-1 3'UTR binding, NRP-1 mRNA stability assay, Wnt/β-catenin signaling pathway analysis, NRP-1 knockdown rescue experiments Biomedicine & pharmacotherapy Medium 29787985
2022 The hematopoietic developmental switch from fetal to adult output is regulated by the Lin28b/let-7 axis via the Polycomb repressor complex 1 (PRC1) component Cbx2; Cbx2 is a downstream effector of Lin28b/let-7 that regulates chromatin modification and transcription factor expression controlling hematopoietic maturation timing. Transcriptomic data mining comparing juvenile and adult HSPCs, gene regulatory network reconstruction, Cbx2-/- mouse hematopoietic analysis, Lin28b/let-7 axis manipulation Cell reports Medium 35385744
2023 ALDH2 directly binds to LIN28B protein, hindering LIN28B binding to ELK3 mRNA and thereby reducing ELK3 mRNA stability and expression, which impairs endothelial barrier function in abdominal aortic aneurysm. Co-immunoprecipitation/molecular binding assay demonstrating ALDH2-LIN28B interaction, LIN28B-ELK3 mRNA binding competition assay, ALDH2 endothelial-specific KD/KO mouse models, endothelial barrier function assays Advanced science Medium 37822152
2016 TRIM71 post-transcriptionally represses Lin28B expression in a ubiquitin-transfer-activity-dependent manner; TRIM71 ubiquitin transfer activity-deficient mutant has no effect on Lin28B levels or cancer cell proliferation/invasion, identifying TRIM71 as an E3 ubiquitin ligase that targets Lin28B for degradation. TRIM71 overexpression with wild-type and ubiquitin-transfer-deficient mutant, Lin28B and HMGA2 expression analysis, NSCLC proliferation and invasion assays, in vivo tumor formation Oncotarget Medium 27821801

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms. Cell 529 22118463
2012 LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression. Nature genetics 322 23042116
2006 Identification and characterization of lin-28 homolog B (LIN28B) in human hepatocellular carcinoma. Gene 254 16971064
2012 Common variation at 6q16 within HACE1 and LIN28B influences susceptibility to neuroblastoma. Nature genetics 228 22941191
2016 SIRT6 Suppresses Pancreatic Cancer through Control of Lin28b. Cell 226 27180906
2011 LIN28B promotes colon cancer progression and metastasis. Cancer research 208 21512136
2014 Lin28b is sufficient to drive liver cancer and necessary for its maintenance in murine models. Cancer cell 172 25117712
2021 NSUN2-mediated RNA 5-methylcytosine promotes esophageal squamous cell carcinoma progression via LIN28B-dependent GRB2 mRNA stabilization. Oncogene 164 34345012
2015 Aberrant regulation of the LIN28A/LIN28B and let-7 loop in human malignant tumors and its effects on the hallmarks of cancer. Molecular cancer 155 26123544
2013 LIN28/LIN28B: an emerging oncogenic driver in cancer stem cells. The international journal of biochemistry & cell biology 140 23420006
2013 LIN28B-mediated expression of fetal hemoglobin and production of fetal-like erythrocytes from adult human erythroblasts ex vivo. Blood 123 23798711
2015 Lin28B/Let-7 Regulates Expression of Oct4 and Sox2 and Reprograms Oral Squamous Cell Carcinoma Cells to a Stem-like State. Cancer research 118 25858147
2013 LIN28B promotes growth and tumorigenesis of the intestinal epithelium via Let-7. Genes & development 112 24142874
2011 LIN28B fosters colon cancer migration, invasion and transformation through let-7-dependent and -independent mechanisms. Oncogene 112 21625210
2015 Lin28b promotes fetal B lymphopoiesis through the transcription factor Arid3a. The Journal of experimental medicine 107 25753579
2016 The oncogenic triangle of HMGA2, LIN28B and IGF2BP1 antagonizes tumor-suppressive actions of the let-7 family. Nucleic acids research 104 26917013
2015 Overexpression of the RNA-binding proteins Lin28B and IGF2BP3 (IMP3) is associated with chemoresistance and poor disease outcome in ovarian cancer. British journal of cancer 102 26158423
2013 miR-26a enhances miRNA biogenesis by targeting Lin28B and Zcchc11 to suppress tumor growth and metastasis. Oncogene 100 24056962
2018 Long noncoding RNA NEAT1, regulated by LIN28B, promotes cell proliferation and migration through sponging miR-506 in high-grade serous ovarian cancer. Cell death & disease 98 30154460
2015 A LIN28B-RAN-AURKA Signaling Network Promotes Neuroblastoma Tumorigenesis. Cancer cell 96 26481147
2020 Control of human hemoglobin switching by LIN28B-mediated regulation of BCL11A translation. Nature genetics 93 31959994
2010 Lin-28B expression promotes transformation and invasion in human hepatocellular carcinoma. Carcinogenesis 89 20525879
2020 LINC00665 promotes breast cancer progression through regulation of the miR-379-5p/LIN28B axis. Cell death & disease 80 31907362
2009 N-Myc regulates expression of pluripotency genes in neuroblastoma including lif, klf2, klf4, and lin28b. PloS one 78 19495417
2012 Lin28b promotes head and neck cancer progression via modulation of the insulin-like growth factor survival pathway. Oncotarget 77 23482325
2011 LIN28B polymorphisms influence susceptibility to epithelial ovarian cancer. Cancer research 77 21482675
2016 The LIN28B/let-7 axis is a novel therapeutic pathway in multiple myeloma. Leukemia 76 27773931
2020 LIN28B promotes the development of neuroendocrine prostate cancer. The Journal of clinical investigation 75 32634132
2020 Pancreatic circulating tumor cell profiling identifies LIN28B as a metastasis driver and drug target. Nature communications 72 32620742
2019 Targeting LIN28B reprograms tumor glucose metabolism and acidic microenvironment to suppress cancer stemness and metastasis. Oncogene 69 30742065
2018 A cancer-testis non-coding RNA LIN28B-AS1 activates driver gene LIN28B by interacting with IGF2BP1 in lung adenocarcinoma. Oncogene 67 30353165
2012 Enforced expression of Lin28b leads to impaired T-cell development, release of inflammatory cytokines, and peripheral T-cell lymphoma. Blood 67 22723554
2017 Inhibition of LIN28B impairs leukemia cell growth and metabolism in acute myeloid leukemia. Journal of hematology & oncology 66 28693523
2014 MUC1-C Induces the LIN28B→LET-7→HMGA2 Axis to Regulate Self-Renewal in NSCLC. Molecular cancer research : MCR 61 25368430
2020 Loss of hnRNPA2B1 inhibits malignant capability and promotes apoptosis via down-regulating Lin28B expression in ovarian cancer. Cancer letters 59 32006618
2015 LIN28B overexpression defines a novel fetal-like subgroup of juvenile myelomonocytic leukemia. Blood 58 26712910
2013 Identification of LIN28B-bound mRNAs reveals features of target recognition and regulation. RNA biology 56 23770886
2020 LIN28B/let-7 control the ability of neonatal murine auditory supporting cells to generate hair cells through mTOR signaling. Proceedings of the National Academy of Sciences of the United States of America 55 32826333
2019 Enhancement of LIN28B-induced hematopoietic reprogramming by IGF2BP3. Genes & development 55 31221665
2018 Decreased LIN28B in preeclampsia impairs human trophoblast differentiation and migration. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 55 30307771
2018 RNA-binding protein LIN28B inhibits apoptosis through regulation of the AKT2/FOXO3A/BIM axis in ovarian cancer cells. Signal transduction and targeted therapy 52 30174831
2016 Lin28b Regulates Fetal Regulatory T Cell Differentiation through Modulation of TGF-β Signaling. Journal of immunology (Baltimore, Md. : 1950) 45 27793996
2015 IKKβ Enforces a LIN28B/TCF7L2 Positive Feedback Loop That Promotes Cancer Cell Stemness and Metastasis. Cancer research 44 25744721
2015 MYCN-driven regulatory mechanisms controlling LIN28B in neuroblastoma. Cancer letters 43 26123663
2022 Follistatin promotes LIN28B-mediated supporting cell reprogramming and hair cell regeneration in the murine cochlea. Science advances 42 35148175
2018 LncRNA H19-elevated LIN28B promotes lung cancer progression through sequestering miR-196b. Cell cycle (Georgetown, Tex.) 42 29950144
2016 Potentially functional polymorphisms in the LIN28B gene contribute to neuroblastoma susceptibility in Chinese children. Journal of cellular and molecular medicine 42 27021521
2018 Long non-coding RNA UFC1 promotes gastric cancer progression by regulating miR-498/Lin28b. Journal of experimental & clinical cancer research : CR 41 29970131
2015 The RNA-binding protein LIN28B regulates developmental timing in the mammalian cochlea. Proceedings of the National Academy of Sciences of the United States of America 40 26139524
2020 LIN28B regulates transcription and potentiates MYCN-induced neuroblastoma through binding to ZNF143 at target gene promotors. Proceedings of the National Academy of Sciences of the United States of America 39 32601179
2020 LIN28B-AS1-IGF2BP1 binding promotes hepatocellular carcinoma cell progression. Cell death & disease 38 32917856
2017 miR-203 enhances let-7 biogenesis by targeting LIN28B to suppress tumor growth in lung cancer. Scientific reports 38 28218277
2019 Osteosarcoma-initiating cells show high aerobic glycolysis and attenuation of oxidative phosphorylation mediated by LIN28B. Cancer science 36 31705593
2010 LIN28B in constitutional delay of growth and puberty. The Journal of clinical endocrinology and metabolism 35 20350940
2011 LIN28B, LIN28A, KISS1, and KISS1R in idiopathic central precocious puberty. BMC research notes 34 21939553
2018 RNA binding protein Lin28B confers gastric cancer cells stemness via directly binding to NRP-1. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 33 29787985
2019 DLL3 is regulated by LIN28B and miR-518d-5p and regulates cell proliferation, migration and chemotherapy response in advanced small cell lung cancer. Biochemical and biophysical research communications 32 31079917
2016 LIN28B Activation by PRL-3 Promotes Leukemogenesis and a Stem Cell-like Transcriptional Program in AML. Molecular cancer research : MCR 32 28011885
2021 LINC01094 promotes pancreatic cancer progression by sponging miR-577 to regulate LIN28B expression and the PI3K/AKT pathway. Molecular therapy. Nucleic acids 31 34631282
2019 Lin28b regulates age-dependent differences in murine platelet function. Blood advances 31 30622145
2015 Lin28B and Let-7 in the Control of Sympathetic Neurogenesis and Neuroblastoma Development. The Journal of neuroscience : the official journal of the Society for Neuroscience 31 26674877
2014 LIN28B promotes colon cancer migration and recurrence. PloS one 30 25360631
2012 Investigation of peripubertal expression of Lin28a and Lin28b in C57BL/6 female mice. Molecular and cellular endocrinology 30 23138112
2023 Structural mechanism of LIN28B nucleosome targeting by OCT4. Molecular cell 29 37327775
2019 LIN28B increases neural crest cell migration and leads to transformation of trunk sympathoadrenal precursors. Cell death and differentiation 29 31601998
2018 A LIN28B Tumor-Specific Transcript in Cancer. Cell reports 29 29466730
2019 miR-152/LIN28B axis modulates high-glucose-induced angiogenesis in human retinal endothelial cells via VEGF signaling. Journal of cellular biochemistry 28 31609010
2020 LIN28B promotes neuroblastoma metastasis and regulates PDZ binding kinase. Neoplasia (New York, N.Y.) 26 32339949
2019 Neoplastic Transformation of Human Mesenchymal Stromal Cells Mediated via LIN28B. Scientific reports 25 31147574
2017 MicroRNA-125b-5p mediates post-transcriptional regulation of hepatitis B virus replication via the LIN28B/let-7 axis. RNA biology 25 28267418
2016 Merlin/NF2-Lin28B-let-7 Is a Tumor-Suppressive Pathway that Is Cell-Density Dependent and Hippo Independent. Cell reports 25 26997273
2013 The human fetal lymphocyte lineage: identification by CD27 and LIN28B expression in B cell progenitors. Journal of leukocyte biology 25 23901121
2020 The KRAS/Lin28B axis maintains stemness of pancreatic cancer cells via the let-7i/TET3 pathway. Molecular oncology 24 33107691
2016 Comparison of the expression and function of Lin28A and Lin28B in colon cancer. Oncotarget 24 27793004
2016 TRIM71 suppresses tumorigenesis via modulation of Lin28B-let-7-HMGA2 signaling. Oncotarget 24 27821801
2011 Metformin may antagonize Lin28 and/or Lin28B activity, thereby boosting let-7 levels and antagonizing cancer progression. Medical hypotheses 24 22129484
2022 Sirt6 inhibits vascular endothelial cell pyroptosis by regulation of the Lin28b/let-7 pathway in atherosclerosis. International immunopharmacology 23 35978508
2023 Early Progression of Abdominal Aortic Aneurysm is Decelerated by Improved Endothelial Barrier Function via ALDH2-LIN28B-ELK3 Signaling. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 22 37822152
2017 Lin28B and miR-142-3p regulate neuronal differentiation by modulating Staufen1 expression. Cell death and differentiation 22 29099484
2015 The role of Lin28b in myeloid and mast cell differentiation and mast cell malignancy. Leukemia 22 25655194
2014 Lin28B expression correlates with aggressive clinicopathological characteristics in breast invasive ductal carcinoma. Cancer biotherapy & radiopharmaceuticals 22 24885919
2022 Developmental maturation of the hematopoietic system controlled by a Lin28b-let-7-Cbx2 axis. Cell reports 21 35385744
2022 The OTUD6B-LIN28B-MYC axis determines the proliferative state in multiple myeloma. The EMBO journal 21 36059274
2021 The LIN28B/TGF-β/TGFBI feedback loop promotes cell migration and tumour initiation potential in cholangiocarcinoma. Cancer gene therapy 21 34548635
2019 Lin28b controls a neonatal to adult switch in B cell positive selection. Science immunology 21 31562190
2017 The correlation between LIN28B gene potentially functional variants and Wilms tumor susceptibility in Chinese children. Journal of clinical laboratory analysis 21 28301057
2014 A potential regulatory loop between Lin28B:miR‑212 in androgen-independent prostate cancer. International journal of oncology 21 25201220
2021 LIN28B alters ribosomal dynamics to promote metastasis in MYCN-driven malignancy. The Journal of clinical investigation 20 34779407
2020 Propofol‑induced miR‑125a‑5p inhibits the proliferation and metastasis of ovarian cancer by suppressing LIN28B. Molecular medicine reports 20 32627014
2018 LIN28B enhanced tumorigenesis in an autochthonous KRASG12V-driven lung carcinoma mouse model. Oncogene 20 29503447
2017 Lin28B facilitates the progression and metastasis of pancreatic ductal adenocarcinoma. Oncotarget 20 28947981
2015 Lin28B over-expression mediates the repression of let-7 by hepatitis B virus X protein in hepatoma cells. International journal of clinical and experimental medicine 20 26628994
2022 lncRNA LUCAT1/ELAVL1/LIN28B/SOX2 Positive Feedback Loop Promotes Cell Stemness in Triple-Negative Breast Cancer. The breast journal 19 35711895
2022 LOC101929709 promotes gastric cancer progression by aiding LIN28B to stabilize c-MYC mRNA. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 19 36284068
2020 LIN28B Underlies the Pathogenesis of a Subclass of Ewing Sarcoma LIN28B Control of EWS-FLI1 Stability. Cell reports 19 32234488
2018 Modulation of LIN28B/Let-7 Signaling by Propranolol Contributes to Infantile Hemangioma Involution. Arteriosclerosis, thrombosis, and vascular biology 19 29724816
2018 The LIN28B-IMP1 post-transcriptional regulon has opposing effects on oncogenic signaling in the intestine. Genes & development 19 30068703
2023 LIN28B promotes cell invasion and colorectal cancer metastasis via CLDN1 and NOTCH3. JCI insight 18 37318881
2023 N6-methyladenosine-mediated overexpression of long noncoding RNA ADAMTS9-AS2 triggers neuroblastoma differentiation via regulating LIN28B/let-7/MYCN signaling. JCI insight 18 37991019
2020 Lin28B/miR-92b Promote the Proliferation, Migration, and Invasion in the Pathogenesis of Preeclampsia via the DKK1/Wnt/β-Catenin Pathway. Reproductive sciences (Thousand Oaks, Calif.) 18 32072603

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