| 2004 |
Human LIN9 (hLin-9) physically binds to pRB (retinoblastoma protein) and cooperates with pRB in flat cell formation and transactivation of an osteoblast-specific reporter gene. hLin-9 associates with partially penetrant pRB mutants that cannot bind E2F but retain transcriptional activation ability, indicating the LIN9-pRB interaction is distinct from E2F-pRB interaction. RNAi knockdown of LIN9 can substitute for loss of pRB in oncogenic transformation of human primary fibroblasts, demonstrating LIN9's tumor-suppressing activity is mediated through pRB. |
Co-immunoprecipitation, RNAi knockdown, reporter gene transactivation assays, flat cell formation assay in Saos-2 cells |
The EMBO journal |
High |
15538385
|
| 2000 |
C. elegans lin-9 functions in an Rb-related pathway that antagonizes receptor tyrosine kinase/Ras signaling to control vulval induction, and is also required for gonadal sheath cell development and male spicule/ray/gonad development. lin-9 encodes a novel protein of 642-644 amino acids with conserved orthologs in Drosophila and vertebrates, founding a new protein family that functions in Rb-related pathways. |
Genetic epistasis analysis, loss-of-function mutant characterization, cDNA cloning and sequence analysis in C. elegans |
Gene |
High |
10974557
|
| 2006 |
Human LIN-9 is required for transcription of G2/M genes and for entry into mitosis. LIN-9 associates with B-MYB, and both LIN-9 and B-MYB bind directly to the promoters of G2/M-regulated genes as shown by chromatin immunoprecipitation. Depletion of LIN-9 by RNAi strongly impairs proliferation and delays G2-to-M progression. Depletion of B-MYB recapitulates the LIN-9 knockdown phenotype, indicating LIN-9 and B-MYB co-activate G2/M gene expression. |
RNAi knockdown, chromatin immunoprecipitation (ChIP), co-immunoprecipitation, proliferation assays, cell cycle analysis in human fibroblasts |
The EMBO journal |
High |
17159899
|
| 2009 |
In F9 embryonal carcinoma cells, B-Myb is found in complexes with Lin-9 and other LINC constituents (but not pocket proteins, which only associate with LINC upon differentiation). B-Myb recruits Lin-9 to the Survivin promoter through multiple Myb-binding sites. Both B-Myb and Lin-9 are required for transcription of G2/M genes (Cyclin B1, Survivin). Loss of Lin-9 causes mitotic arrest in F9 cells. |
Co-immunoprecipitation, chromatin immunoprecipitation, RNAi knockdown, reporter assays, cell cycle analysis |
Oncogene |
High |
19252525
|
| 2009 |
Lin9 depletion in zebrafish embryos causes accumulation of cells in mitosis followed by apoptosis, particularly in the developing central nervous system. A cohort of Lin9-regulated mitotic genes required for mitotic entry, metaphase/anaphase transition, and cytokinesis was identified, establishing LIN9 as an essential regulator of mitosis in vertebrate development. |
Antisense morpholino knockdown in zebrafish, flow cytometry, confocal microscopy, gene expression profiling |
The Journal of biological chemistry |
High |
19278998
|
| 2010 |
Lin9 is an essential core subunit of the mammalian DREAM complex. Genetic knockout of Lin9 is lethal in early embryonic development and in adult mice. Loss of Lin9 abolishes proliferation and causes multiple mitotic and cytokinesis defects due to loss of expression of mitotic genes including Plk1, Aurora A, and Kif20a. Lin9 heterozygous mice are more susceptible to oncogenic c-Raf-induced lung tumorigenesis, indicating haploinsufficient tumor suppressor function. |
Conditional and constitutive knockout mouse models, gene expression analysis, proliferation assays, tumor induction by oncogenic c-Raf |
Molecular and cellular biology |
High |
20404087
|
| 2011 |
Loss of LIN9 triggers premature senescence via upregulation of p16(INK4a) and p21(Waf1), implicating the pRB and p53 tumor suppressor pathways. SV40 large T antigen can overcome this senescence. LIN9-null cells that escape senescence exhibit chromosomal instability due to compromised mitotic fidelity, and SV40 LT-expressing LIN9-null cells grow anchorage-independently in soft agar. |
Gene knockout in mouse cells, immunoblotting for p16/p21, soft agar anchorage-independent growth assay, chromosomal instability analysis |
Oncogene |
High |
21860417
|
| 2011 |
In hepatocellular carcinoma cells, LIN9 forms a complex with MYBL2 (B-Myb) termed LINC. The integrity of the MYBL2-LIN9 complex is required for survival of DNA-damaged p53-null cells. Doxorubicin treatment causes LIN9 dissociation from MYBL2 in p53-positive cells (leading to p21(WAF1) upregulation) but increases MYBL2-LIN9 complexes in p53-null cells. siRNA-mediated silencing of MYBL2/LINC reduces proliferation and induces apoptosis. |
Co-immunoprecipitation, siRNA knockdown, proliferation assays, apoptosis assays, immunoblotting in HCC cell lines |
Hepatology (Baltimore, Md.) |
Medium |
21480327
|
| 2014 |
Cyclin E1/Cdk3 phosphorylates LIN-9 on Threonine-96. Mutation of Thr-96 to alanine inhibits activation of cyclin A2 and B1 promoters, whereas a phosphomimetic Asp mutant strongly activates these promoters and triggers accelerated entry into G2/M phase. This establishes a role for cyclin E1 in S/G2 phase through LIN-9 phosphorylation to induce expression of subsequent cyclins. |
In vitro kinase assay, site-directed mutagenesis (T96A and T96D mutants), promoter reporter assays, cell cycle analysis in 293T cells |
PloS one |
High |
24475316
|
| 2017 |
LIN9 is a direct transcriptional target of BET bromodomain proteins in triple-negative breast cancer cells. BET inhibition suppresses LIN9 expression, leading to prolonged mitotic progression and mitotic cell death (mitotic catastrophe). LIN9 mediates the effects of BET proteins on mitosis. The LIN9 gene lacks a super-enhancer but is amplified or overexpressed in the majority of TNBCs. |
Live cell imaging, BET inhibitor treatment, RNAi knockdown of LIN9, ChIP for BET proteins at LIN9 locus, gene expression analysis in TNBC cell lines |
Cancer research |
High |
28807940
|
| 2019 |
LIN9 promotes paclitaxel resistance in triple-negative breast cancer cells at least in part by directly regulating the microtubule-binding protein CCSAP. LIN9 expression is elevated in paclitaxel-resistant TNBC cell lines. Knockdown of LIN9 or BETi treatment reduces LIN9 expression, promotes multinucleated cell formation, and restores paclitaxel sensitivity. |
qRT-PCR, Western blot, siRNA knockdown, MTS cell viability assay, flow cytometry for apoptosis in TNBC cell lines and resistant sublines |
Science China. Life sciences |
Medium |
31420851
|
| 2020 |
LIN9 transcriptionally regulates NEK2 (NIMA-related kinase 2) expression in taxane-resistant breast cancer cells. Elevated LIN9 in taxane-resistant cells sustains NEK2 expression and centrosome separation. Genetic or pharmacologic inhibition of LIN9 (via BET inhibitors) or NEK2 in combination with paclitaxel synergistically induces mitotic abnormalities in nearly 100% of cells and restores paclitaxel sensitivity in vitro and in vivo, including in patient-derived xenografts. |
Computational target identification, genetic knockdown, pharmacologic NEK2 inhibition, in vitro mitosis assays, in vivo TNBC xenograft and PDX models |
Cancer research |
High |
32054769
|
| 2024 |
In vascular smooth muscle cells, IL-1β (downstream of NLRP3 activation) promotes BRD4 recruitment to the LIN9 locus, enhancing LIN9 expression. LIN9 then binds to the promoter region of AURKA, promoting its transcription and subsequently upregulating FOXM1, thereby mediating VSMC proliferation, migration, and paclitaxel resistance. JQ1 (BET inhibitor) inhibits BRD4-mediated LIN9 upregulation and shows synergy with PTX. |
RNA sequencing, ChIP assay (LIN9 binding to AURKA promoter, BRD4 binding to LIN9 locus), siRNA knockdown, in vivo rat restenosis model |
Journal of translational medicine |
High |
39334121
|
| 2024 |
E2F4 physically interacts with LIN9 in hepatocellular carcinoma cells, as demonstrated by co-immunoprecipitation, immunofluorescence co-localization, and bimolecular fluorescence complementation assays. E2F4 promotes HCC cell proliferation and SUMOylation via LIN9; rescue experiments showed LIN9 facilitates SUMOylation and proliferation driven by E2F4. |
Co-immunoprecipitation, immunofluorescence co-localization, bimolecular fluorescence complementation, soft agar assay, Transwell migration assay, Western blotting |
International journal of oncology |
Medium |
39239750
|
| 2025 |
YARS (tyrosyl tRNA synthetase) binds to the LIN9 promoter and facilitates RNA polymerase II recruitment and phosphorylation, and deposition of activating epigenetic marks. YARS interacts with the Trim28 transcriptional regulator. During senescence escape, YARS activates LIN9 expression; both YARS and LIN9 are necessary for the proliferation of senescence-escaping cells. |
ChIP assay (YARS binding at LIN9 promoter), co-immunoprecipitation (YARS-Trim28 interaction), RNA polymerase II phosphorylation analysis, epigenetic mark analysis, siRNA knockdown of YARS and LIN9 |
The FEBS journal |
Medium |
39756023
|