Affinage

DLX6

Homeobox protein DLX-6 · UniProt P56179

Length
175 aa
Mass
19.7 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DLX6 encodes a homeodomain transcription factor that, together with its paralog DLX5, acts as a master regulator of craniofacial patterning, limb morphogenesis, inner ear development, GABAergic interneuron differentiation, and uterine adenogenesis. In the mandibular arch, DLX6 functions downstream of endothelin-1/Ednra signaling to bind homeodomain sites in the dHAND branchial arch enhancer, specifying lower jaw identity—loss of both Dlx5 and Dlx6 transforms the mandible into a maxilla-like structure (PMID:12434331, PMID:11711438). During limb development, DLX5/DLX6 operate upstream of Wnt5a to organize the apical ectodermal ridge and regulate a Dlx–Msx–BMP feedback loop controlling digit formation, while in endochondral bone they promote chondrocyte hypertrophy cell-autonomously (PMID:26685160, PMID:23382810, PMID:19956613). DLX5/DLX6 are also required for tangential migration and maturation of parvalbumin-positive cortical interneurons, vestibular morphogenesis, posterior axis patterning, and uterine gland formation, and a loss-of-function LINE-1 insertion in the DLX6 homeodomain causes a Pierre Robin–like craniofacial syndrome in dogs (PMID:20392955, PMID:16900517, PMID:26512061, PMID:24699068).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2000 High

    Establishing that DLX family members cross-regulate one another through a conserved intergenic enhancer resolved how Dlx5/Dlx6 transcription is controlled in the forebrain and linked Dlx gene regulation to an autoregulatory/cross-regulatory circuit.

    Evidence Transgenic reporter assay, EMSA, cotransfection, Dlx1/Dlx2 double-mutant epistasis in mouse forebrain

    PMID:10632600

    Open questions at the time
    • Whether additional trans-acting factors beyond Dlx1/2 regulate the intergenic enhancer in vivo
    • Whether the cross-regulatory mechanism operates identically in non-forebrain tissues
  2. 2001 High

    Identifying DLX6 as a direct downstream effector of ET-1/Ednra signaling that binds the dHAND enhancer placed DLX6 within a signaling cascade governing craniofacial morphogenesis.

    Evidence Protein binding assay comparing wild-type and EdnrA-mutant branchial arch extracts; enhancer analysis in mouse

    PMID:11711438

    Open questions at the time
    • Whether DLX6 binding to the dHAND enhancer is direct or requires co-factors
    • The complete set of DLX6 direct transcriptional targets in the mandibular arch
  3. 2002 High

    Double knockout of Dlx5 and Dlx6 revealed their combined essential roles in jaw identity (homeotic mandible-to-maxilla transformation) and limb outgrowth (SHFM phenotype), establishing them as homeotic-like regulators in Hox-free territories.

    Evidence Dlx5/Dlx6 double knockout mice with morphological, histological, and skeletal analysis; transgenic Dlx5 rescue of limb phenotype

    PMID:12000792 PMID:12434331

    Open questions at the time
    • The relative individual contributions of Dlx5 versus Dlx6 to each phenotype
    • Downstream target genes mediating the jaw homeotic transformation
  4. 2006 High

    Extending the phenotypic spectrum, Dlx5/Dlx6 loss was shown to abolish dorsal otic structures and to positively regulate chondrogenesis with functional redundancy, broadening their roles to inner ear patterning and endochondral skeleton formation.

    Evidence Double KO mouse vestibular phenotype with in situ hybridization; limb bud mesenchymal differentiation assay with domain mutagenesis

    PMID:16900517 PMID:17027239

    Open questions at the time
    • Whether DLX5 and DLX6 have distinct domain-specific functions despite overlapping activity
    • Direct transcriptional targets in otic epithelium
  5. 2009 High

    Chondrocyte-specific transgenic rescue demonstrated that DLX5/DLX6 drive chondrocyte hypertrophy cell-autonomously, not through indirect paracrine signals.

    Evidence Col2a1-Dlx5 transgenic mice rescuing Dlx5/6-null chondrocyte defects; histological analysis

    PMID:19956613

    Open questions at the time
    • Direct DLX5/6 target genes in hypertrophic chondrocytes
    • Whether DLX6 alone is sufficient for the cell-autonomous rescue
  6. 2010 High

    Loss of Dlx5/Dlx6 in GABAergic progenitors was shown to impair tangential migration and maturation of parvalbumin-positive cortical interneurons, with haploinsufficiency causing seizures, connecting DLX5/6 to cortical circuit function.

    Evidence Conditional/constitutive knockout, interneuron transplantation, immunohistochemistry, electrophysiology in mouse

    PMID:20392955

    Open questions at the time
    • Whether DLX6 alone versus DLX5 alone contributes to interneuron migration
    • Mechanism by which DLX5/6 regulate CXCR4 expression
  7. 2010 High

    A SNP in the ultraconserved I56i intergenic enhancer was shown to reduce Dlx protein binding and enhancer activity in ganglionic eminences, and affinity purification identified GTF2I as a novel Dlx regulatory partner, linking enhancer variation to potential neurodevelopmental phenotypes.

    Evidence Transgenic reporter, in vitro binding, affinity purification in mouse

    PMID:20702565

    Open questions at the time
    • In vivo significance of the SNP in human neurodevelopmental disease
    • Whether GTF2I directly interacts with DLX proteins or acts through the enhancer alone
  8. 2011 High

    Multiple studies in 2011 expanded DLX5/6 functions to a Hand2–Dlx5/6 negative feedback loop in mandible morphogenesis, ectethmoid nasal capsule formation from the anterior neural fold, striatal/amygdalar gene regulation by Dlx6 alone, and ovarian follicle maintenance via reciprocal Dlx5/Foxl2 regulation.

    Evidence Conditional KO and triple-mutant epistasis in mouse mandible; siRNA and grafting in chick neurula; Dlx6-LacZ knockin with expression array; heterozygous mouse ovarian phenotyping

    PMID:21270050 PMID:21452241 PMID:21505076 PMID:21558373

    Open questions at the time
    • Whether DLX6 has unique non-redundant functions in the striatum independent of DLX5
    • Direct transcriptional targets of DLX5/6 in granulosa cells
    • Whether the Hand2–Dlx feedback loop operates in human craniofacial development
  9. 2013 High

    A Dlx–Msx–BMP regulatory loop was delineated in the limb, with DLX5/6 epistatic over Msx2 in AER cells and operating via BMP in limb mesoderm, and Dlx5/6 were shown to be dispensable for Edn1/Ednra-mediated pharyngeal arch artery patterning.

    Evidence Triple mutant (Msx1;Dlx5;Dlx6) mice with ChIP; Dlx5/6 and Ednra KO with neural crest lineage tracing

    PMID:23382810 PMID:23933587

    Open questions at the time
    • Complete catalog of DLX5/6-bound cis-regulatory elements in the AER
    • Whether additional BMP-independent pathways link DLX5/6 to limb patterning
  10. 2014 Medium

    A LINE-1 insertion truncating the DLX6 homeodomain was identified as the causative mutation for Pierre Robin–like craniofacial defects in dogs, providing the first direct genetic link between DLX6 coding mutation and a Mendelian-like craniofacial phenotype.

    Evidence GWAS, sequencing, micro-CT in Nova Scotia Duck Tolling Retrievers

    PMID:24699068

    Open questions at the time
    • Functional validation by allelic rescue or in vitro assay of the truncated protein
    • Whether analogous DLX6 mutations exist in human Pierre Robin sequence patients
  11. 2015 High

    DLX5/6 were positioned upstream of Wnt5a in AER organization and shown to be required for uterine adenogenesis, broadening their developmental regulatory network to Wnt signaling and reproductive tract morphogenesis.

    Evidence Double KO limb analysis with ex vivo Wnt5a rescue; conditional uterine KO (Pgr-Cre) with histology and expression analysis

    PMID:26512061 PMID:26685160

    Open questions at the time
    • Whether DLX5/6 directly activate Wnt5a transcription or act through intermediaries
    • Target genes downstream of DLX5/6 in uterine gland progenitors
  12. 2019 Medium

    DLX5/6 were shown to antagonize cell proliferation at the G1/S checkpoint across multiple cell types, and their conditional loss in GABAergic neurons yielded reduced anxiety, lower adiposity, and extended lifespan, revealing systemic metabolic consequences of interneuron-specific DLX5/6 function.

    Evidence Overexpression with BrdU/flow cytometry in multiple cell lines; Vgat-Cre conditional KO with behavioral and metabolic phenotyping

    PMID:31041891 PMID:31514171

    Open questions at the time
    • Whether the cell cycle effect is direct transcriptional regulation or indirect
    • The neural circuit mechanism linking GABAergic DLX5/6 loss to metabolic and aging phenotypes
    • Whether posterior axis defects in Dlx5/6 null mice involve the same cell cycle mechanism
  13. 2023 Medium

    DLX6 was identified as a transcriptional activator of ATG7 in glioma via ChIP-validated promoter binding, placing DLX6 in a DANCR/miR-33b/DLX6/ATG7 axis promoting autophagy, extending DLX6's transcriptional targets beyond developmental contexts.

    Evidence ChIP assay, dual-luciferase reporter, siRNA knockdown, xenograft model in glioma cells

    PMID:36601767

    Open questions at the time
    • Whether DLX6-dependent ATG7 activation occurs in normal developmental tissues
    • Genome-wide binding profile of DLX6 in cancer cells

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the genome-wide direct transcriptional targets of DLX6 in developmental and disease contexts, the non-redundant functions of DLX6 versus DLX5, the structural basis for DLX6 homeodomain target specificity, and whether human DLX6 mutations cause Mendelian craniofacial or neurodevelopmental disorders.
  • No genome-wide ChIP-seq for DLX6 in primary developmental tissues
  • No crystal or cryo-EM structure of DLX6 homeodomain–DNA complex
  • No confirmed pathogenic DLX6 coding variants in human genetic disease

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-1266738 Developmental Biology 8 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 3
Partners
DLX1DLX2DLX5GTF2IHAND2MSX2

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Combined targeted inactivation of Dlx5 and Dlx6 in mice results in severe craniofacial, axial, and appendicular skeletal abnormalities phenocopying split-hand/split-foot malformation (SHFM), and transgenic overexpression of Dlx5 in the apical ectodermal ridge of Dlx5/6 null mice fully rescues limb outgrowth, establishing Dlx5/Dlx6 as critical regulators of mammalian limb development. Targeted gene knockout (loss-of-function) and transgenic rescue in mice Genes & development High 12000792
2002 Simultaneous inactivation of Dlx5 and Dlx6 in mice transforms the lower jaw into an upper jaw structure, constituting a homeotic-like transformation in the Hox-free mandibular arch, establishing Dlx5/Dlx6 as homeotic regulators of jaw identity. Double knockout mouse; morphological and histological analysis Genesis (New York, N.Y. : 2000) High 12434331
2000 Dlx1 and Dlx2 proteins bind conserved homeodomain binding sites in the Dlx5/Dlx6 intergenic enhancer region to cross-regulate Dlx5 and Dlx6 expression in the developing forebrain; reporter transgene activity is drastically reduced in Dlx1/Dlx2 double mutants, and Dlx protein binding to the enhancer was confirmed by cotransfection and DNA-protein binding experiments. Transgenic reporter assay, cotransfection, DNA-protein binding (EMSA/binding assay), double-mutant epistasis The Journal of neuroscience High 10632600
2001 Dlx6 protein binds to four homeodomain binding sites in the dHAND branchial arch enhancer in an endothelin-1 (ET-1)/endothelin receptor A (EdnrA)-dependent manner, linking ET-1 signaling to dHAND transcription during craniofacial morphogenesis; Dlx6 expression is down-regulated in EdnrA mutant branchial arches. Protein binding comparison between EdnrA mutant and wild-type branchial arch extracts; enhancer analysis; genetic epistasis (EdnrA mutant mice) Genes & development High 11711438
2010 Simultaneous deletion of Dlx5 and Dlx6 in mice reduces tangential migration of Lhx6+ and Mafb+ interneurons to the cortex (associated with reduced CXCR4 expression) and preferentially reduces the number of mature parvalbumin+ interneurons, while Dlx5/6+/- heterozygous mice show spontaneous electrographic seizures and reduced gamma oscillations. Conditional/constitutive knockout, interneuron transplantation, immunohistochemistry, electrophysiology The Journal of neuroscience High 20392955
2006 Loss-of-function of Dlx5 and Dlx6 in mice causes failure of dorsal otic derivatives (semicircular ducts, utricle, saccule, endolymphatic duct) to form, while otic induction initiates normally; Dlx5/6 influence vestibular cell fates by restricting Pax2 and activating Gbx2 and Bmp4 expression domains. Double knockout mouse, gene expression analysis (in situ hybridization) Genesis (New York, N.Y. : 2000) High 16900517
2011 Hand2, a bHLH transcription factor, represses Dlx5 and Dlx6 expression in the distal mandibular arch ectomesenchyme following Dlx5/Dlx6-mediated induction of Hand2, establishing a negative-feedback loop; failure to repress Dlx5/Dlx6 upregulates Runx2, causes aberrant bone formation, and results in aglossia. Conditional knockout, expression analysis, genetic epistasis Development (Cambridge, England) High 21558373
2006 Dlx5 and Dlx6 are functionally redundant positive regulators of chondrogenesis in the limb; limb bud mesenchymal cells from Dlx5/6 null embryos show reduced chondrogenesis, and expression of either gene stimulates chondroblast differentiation. Despite divergent amino- and carboxyl-terminal domains, Dlx5 and Dlx6 have overlapping biological function in chondrogenesis through distinct domain requirements. Limb bud mesenchymal cell differentiation assay (in vitro), domain deletion/mutation analysis, Dlx5/6 null embryo analysis Mechanisms of development High 17027239
2009 Dlx5 functions as a cell-autonomous regulator of chondrocyte hypertrophy, demonstrated by chondrocyte-specific Col2a1-Dlx5 transgenic mice showing accelerated hypertrophy and mineralization, and this transgene rescuing Dlx5/6 null chondrocyte differentiation defects. Dlx5 and Dlx6 are functionally equivalent in the endochondral skeleton. Chondrocyte-specific transgenic overexpression; rescue of Dlx5/6 null phenotype; histological analysis PloS one High 19956613
2010 A single-nucleotide polymorphism (SNP) within the ultraconserved I56i enhancer in the Dlx5/Dlx6 intergenic region reduces Dlx protein binding affinity to their recognition site in vitro, reduces transcriptional activation of the enhancer by Dlx proteins, and decreases I56i enhancer activity predominantly in medial and caudal ganglionic eminences. Additionally, affinity purification using I56i sequences identified GTF2I (general transcription factor 2I) as a novel regulator of Dlx gene expression. Transgenic reporter assay, in vitro binding assay (affinity purification), transcriptional activation assay Development (Cambridge, England) High 20702565
2011 Dlx6 is required for molecular properties of the striatum and central nucleus of the amygdala; Dlx6 mutants show reduced expression of Golf, RXRγ, Tiam2 in the striatum and reduced Dlx5 in the central nucleus of the amygdala. Unlike other Dlx genes, Dlx6 expression is not readily observed in tangentially migrating interneurons. Dlx6 null (LacZ knockin) mouse; RNA expression array; immunohistochemistry; in situ hybridization The Journal of comparative neurology Medium 21452241
2011 Allelic reduction of Dlx5 and Dlx6 in mice causes a primary ovarian insufficiency (POI)-like phenotype with reduced fertility and early follicular exhaustion; a reciprocal regulation exists between Dlx5 and Foxl2 in granulosa cells, and allelic reduction of Dlx5/6 results in upregulation of Foxl2 in the ovary. Heterozygous mouse model, granulosa cell line experiments, gene expression analysis Human molecular genetics Medium 21505076
2013 Dlx5 and Dlx6 regulate a Dlx-Msx regulatory loop involving BMP molecules during limb development: in anterior limb mesoderm, a non-cell autonomous Msx-Dlx regulatory loop involves BMP through the AER; in AER cells Dlx5 and Dlx6 regulate Msx2 cell-autonomously. Triple mutant (Msx1;Dlx5;Dlx6) mice exhibit hallmark anomalies of Msx1;Msx2 double mutants, revealing epistatic roles of Dlx5 and Dlx6 over Msx2. Triple knockout mice, ChIP, qPCR, bioinformatics, genetic epistasis PloS one High 23382810
2013 Edn1/Ednra signaling regulates neural crest differentiation for pharyngeal arch artery patterning through a Dlx5/Dlx6-independent mechanism; Dlx5/Dlx6 knockout does not significantly affect pharyngeal arch artery or coronary artery development, placing Dlx5/Dlx6 downstream of Edn1/Ednra specifically in jaw identity but not great vessel formation. Dlx5/Dlx6 knockout mice, Ednra knockout mice, neural crest cell lineage tracing (Wnt1-Cre), immunostaining Mechanisms of development High 23933587
2015 Dlx5 and Dlx6 control uterine adenogenesis; conditional inactivation in the endometrium (using Pgr-Cre) results in sterility, very few uterine glands, and reduced expression of Foxa2 and Msx1, establishing Dlx5/Dlx6 as required for uterine gland formation and epithelial remodeling during implantation. Conditional knockout (Pgr-Cre), histology, gene expression analysis Human molecular genetics High 26512061
2015 In Dlx5/6 double knockout hindlimbs, the apical ectodermal ridge (AER) has reduced Wnt5a expression, scattered β-catenin-responsive cells, and altered cell polarity; exogenous Wnt5a restores AER stratification and marker expression, placing Dlx5/Dlx6 upstream of Wnt5a signaling in AER organization and ectrodactyly. Double knockout mouse, ex vivo limb culture with Wnt5a addition, gene expression analysis, immunofluorescence Human molecular genetics High 26685160
2019 Dlx5 and Dlx6 expression antagonizes cell proliferation by reducing the proportion of cells in S-phase and affecting cell cycle length in multiple cell types, without inducing apoptosis, suggesting a lineage-independent cell cycle regulatory function at the G1/S checkpoint to facilitate differentiation. Overexpression in multiple cell lines, cell cycle analysis (BrdU/flow cytometry) BMC molecular and cell biology Medium 31041891
2019 Conditional inactivation of Dlx5/Dlx6 in all GABAergic interneurons (Vgat-Cre mice) results in reduced anxiety-like behavior, reduced obsessive-compulsive activities, body weight reduction at 20 months (due to loss of adipose tissue), and a 33% longer median survival with improved hallmarks of biological aging. Conditional knockout (Vgat-Cre), behavioral analysis, metabolic phenotyping, survival analysis Aging Medium 31514171
2011 Dlx5 and Dlx6 expression in the anterior neural fold (NF-ZA territory) is required for ectethmoid nasal capsule formation; siRNA-mediated downregulation in chick neurula or surgical removal of the NF-ZA territory prevents ectethmoid formation without affecting the mesethmoid, and NF-ZA grafting produces an ectopic ectethmoid. siRNA knockdown in chick, surgical ablation/grafting, mouse double KO, in situ hybridization Development (Cambridge, England) High 21270050
2019 Dlx5/Dlx6 expression at the neural plate border is required for posterior axis formation; Dlx5/6 inactivation in mouse results in open thoracic and lumbar vertebral arches and failure of epaxial muscle formation; zebrafish dlx5a/6a morphants show posterior neural tube defects with altered neural crest cell adhesion molecule expression and motoneuronal development defects. Mouse double KO, zebrafish morpholino knockdown, neural crest cell analysis, in situ hybridization PloS one Medium 30889190
2014 A LINE-1 insertion within the DLX6 homeodomain in Nova Scotia Duck Tolling Retrievers introduces a premature stop codon, causing cleft palate, shortened mandible, and tongue displacement phenotypically similar to Pierre Robin sequence, establishing DLX6 loss-of-function as causative for craniofacial defects in this canine model. Genome-wide association study, sequencing (LINE-1 insertion identification), micro-CT, functional prediction PLoS genetics Medium 24699068
2020 DLX6 promotes proliferation and inhibits apoptosis in oral squamous cell carcinoma cells; microarray analysis and Western blotting indicate DLX6 may regulate OSCC cell proliferation through the EGFR-CCND1 axis. siRNA knockdown in oral cancer cell lines, clone formation, proliferation and apoptosis assays, microarray, Western blot Oral diseases Low 33215805
2023 In glioma cells, lncRNA DANCR sponges miR-33b to upregulate DLX6 protein, which in turn transcriptionally activates ATG7 (confirmed by ChIP assay), promoting autophagy and proliferation via the DANCR/miR-33b/DLX6/ATG7 axis. Dual-luciferase reporter assay, ChIP assay, siRNA knockdown, Western blot, in vivo xenograft Oncology reports Medium 36601767
2020 DLX6-AS1 lncRNA forms a triplex structure with the DLX6 gene promoter region via interaction with p300/E2F1 acetyltransferase complex, promoting DLX6 expression and endometrial cancer progression. Dual-luciferase reporter assay, ChIP, RNA-protein interaction assay, xenograft mouse model Journal of cellular and molecular medicine Medium 32951317
2024 DLX6-AS1 lncRNA is upregulated by BMP9 in dental pulp cells and promotes odonto/osteogenic differentiation by sponging miR-128-3p, which targets MAPK14; RNA immunoprecipitation and dual luciferase reporter assays confirmed direct interactions between DLX6-AS1, miR-128-3p, and MAPK14. qRT-PCR, RNA immunoprecipitation, dual luciferase reporter assay, siRNA/overexpression, alkaline phosphatase/alizarin red staining International endodontic journal Medium 38973098

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 The Dlx5 and Dlx6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development. Genes & development 338 12000792
2000 A highly conserved enhancer in the Dlx5/Dlx6 intergenic region is the site of cross-regulatory interactions between Dlx genes in the embryonic forebrain. The Journal of neuroscience : the official journal of the Society for Neuroscience 276 10632600
2002 Jaw transformation with gain of symmetry after Dlx5/Dlx6 inactivation: mirror of the past? Genesis (New York, N.Y. : 2000) 155 12434331
2010 Dlx5 and Dlx6 regulate the development of parvalbumin-expressing cortical interneurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 139 20392955
2001 Role of Dlx6 in regulation of an endothelin-1-dependent, dHAND branchial arch enhancer. Genes & development 129 11711438
2015 Expression of long non-coding RNA DLX6-AS1 in lung adenocarcinoma. Cancer cell international 73 26052251
2011 Downregulation of Dlx5 and Dlx6 expression by Hand2 is essential for initiation of tongue morphogenesis. Development (Cambridge, England) 73 21558373
2019 Down-regulated lncRNA DLX6-AS1 inhibits tumorigenesis through STAT3 signaling pathway by suppressing CADM1 promoter methylation in liver cancer stem cells. Journal of experimental & clinical cancer research : CR 66 31171015
2017 Long non-coding RNA DLX6-AS1 aggravates hepatocellular carcinoma carcinogenesis by modulating miR-203a/MMP-2 pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 66 29145165
2019 DLX6-AS1/miR-204-5p/OCT1 positive feedback loop promotes tumor progression and epithelial-mesenchymal transition in gastric cancer. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 64 31463827
2019 Long noncoding RNA DLX6-AS1 promotes tumorigenesis by modulating miR-497-5p/FZD4/FZD6/Wnt/β-catenin pathway in pancreatic cancer. Cancer management and research 62 31118816
2018 LncRNA DLX6-AS1/miR-129-5p/DLK1 axis aggravates stemness of osteosarcoma through Wnt signaling. Biochemical and biophysical research communications 59 30442366
2010 An SNP in an ultraconserved regulatory element affects Dlx5/Dlx6 regulation in the forebrain. Development (Cambridge, England) 58 20702565
2020 Knockdown of LncRNA DLX6-AS1 inhibits HK-2 cell pyroptosis via regulating miR-223-3p/NLRP3 pathway in lipopolysaccharide-induced acute kidney injury. Journal of bioenergetics and biomembranes 57 32666494
2018 Long noncoding RNA DLX6-AS1 accelerates the glioma carcinogenesis by competing endogenous sponging miR-197-5p to relieve E2F1. Gene 57 30366080
2017 Long noncoding RNA DLX6-AS1 promotes renal cell carcinoma progression via miR-26a/PTEN axis. Cell cycle (Georgetown, Tex.) 57 28881158
2020 LncRNA DLX6-AS1 Contributes to Epithelial-Mesenchymal Transition and Cisplatin Resistance in Triple-negative Breast Cancer via Modulating Mir-199b-5p/Paxillin Axis. Cell transplantation 50 32686982
2019 Exosomal long non-coding RNA DLX6-AS1 as a potential diagnostic biomarker for non-small cell lung cancer. Oncology letters 49 31612030
2019 Long noncoding RNA DLX6-AS1 promotes liver cancer by increasing the expression of WEE1 via targeting miR-424-5p. Journal of cellular biochemistry 48 30805988
2018 Knockdown of lncRNA DLX6-AS1 inhibits cell proliferation, migration and invasion while promotes apoptosis by downregulating PRR11 expression and upregulating miR-144 in non-small cell lung cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 47 30551440
2006 Dlx5 and Dlx6 homeobox genes are required for specification of the mammalian vestibular apparatus. Genesis (New York, N.Y. : 2000) 45 16900517
2018 LncRNA DLX6-AS1 promoted cancer cell proliferation and invasion by attenuating the endogenous function of miR-181b in pancreatic cancer. Cancer cell international 44 30250401
2014 A LINE-1 insertion in DLX6 is responsible for cleft palate and mandibular abnormalities in a canine model of Pierre Robin sequence. PLoS genetics 44 24699068
2007 DLX5 and DLX6 expression is biallelic and not modulated by MeCP2 deficiency. American journal of human genetics 43 17701895
2001 A zebrafish forebrain-specific zinc finger gene can induce ectopic dlx2 and dlx6 expression. Developmental biology 43 11180958
2019 Long noncoding RNA DLX6-AS1 promotes cell growth and invasiveness in bladder cancer via modulating the miR-223-HSP90B1 axis. Cell cycle (Georgetown, Tex.) 42 31615303
2004 Developmental regulation of EVF-1, a novel non-coding RNA transcribed upstream of the mouse Dlx6 gene. Gene expression patterns : GEP 42 15183307
2021 Exosomal DLX6-AS1 from hepatocellular carcinoma cells induces M2 macrophage polarization to promote migration and invasion in hepatocellular carcinoma through microRNA-15a-5p/CXCL17 axis. Journal of experimental & clinical cancer research : CR 41 34039401
2019 LncRNA DLX6-AS1 promotes the proliferation, invasion, and migration of non-small cell lung cancer cells by targeting the miR-27b-3p/GSPT1 axis. OncoTargets and therapy 41 31190891
2019 Long noncoding RNA DLX6-AS1 promotes breast cancer progression via miR-505-3p/RUNX2 axis. European journal of pharmacology 40 31705901
2022 cAMP-response element binding protein mediates podocyte injury in diabetic nephropathy by targeting lncRNA DLX6-AS1. Metabolism: clinical and experimental 37 35093327
2019 Dlx5 and Dlx6 expression in GABAergic neurons controls behavior, metabolism, healthy aging and lifespan. Aging 36 31514171
2019 The up-regulated lncRNA DLX6-AS1 in colorectal cancer promotes cell proliferation, invasion and migration via modulating PI3K/AKT/mTOR pathway. European review for medical and pharmacological sciences 36 31646562
2019 The lncRNA DLX6-AS1 promoted cell proliferation, invasion, migration and epithelial-to-mesenchymal transition in bladder cancer via modulating Wnt/β-catenin signaling pathway. Cancer cell international 36 31787849
2010 Deletion of an enhancer near DLX5 and DLX6 in a family with hearing loss, craniofacial defects, and an inv(7)(q21.3q35). Human genetics 36 19707792
2019 LncRNA DLX6-AS1 promotes tumor proliferation and metastasis in osteosarcoma through modulating miR-641/HOXA9 signaling pathway. Journal of cellular biochemistry 35 30838699
2020 Long Noncoding RNA DLX6-AS1 Promotes the Progression in Cervical Cancer by Targeting miR-16-5p/ARPP19 Axis. Cancer biotherapy & radiopharmaceuticals 32 32077747
2019 DLX6-AS1 promotes cell proliferation, migration and EMT of gastric cancer through FUS-regulated MAP4K1. Cancer biology & therapy 30 31591939
2020 Long non-coding RNA DLX6-AS1 facilitates bladder cancer progression through modulating miR-195-5p/VEGFA signaling pathway. Aging 29 32756011
2019 Long noncoding RNA DLX6-AS1 promotes neuroblastoma progression by regulating miR-107/BDNF pathway. Cancer cell international 29 31787850
2011 Dlx6 regulates molecular properties of the striatum and central nucleus of the amygdala. The Journal of comparative neurology 29 21452241
2015 Dlx5 and Dlx6 control uterine adenogenesis during post-natal maturation: possible consequences for endometriosis. Human molecular genetics 28 26512061
2020 LncRNA DLX6-AS1 aggravates the development of ovarian cancer via modulating FHL2 by sponging miR-195-5p. Cancer cell international 27 32774164
2019 LncRNA DLX6-AS1 increases the expression of HIF-1α and promotes the malignant phenotypes of nasopharyngeal carcinoma cells via targeting MiR-199a-5p. Molecular genetics & genomic medicine 26 31782911
2021 DLX6-AS1: a putative lncRNA candidate in multiple human cancers. Expert reviews in molecular medicine 25 34823630
2013 BMP-mediated functional cooperation between Dlx5;Dlx6 and Msx1;Msx2 during mammalian limb development. PloS one 25 23382810
2009 Expression analysis and mutation detection of DLX5 and DLX6 in autism. Brain & development 24 19195802
2020 Long non-coding RNA DLX6-AS1 mediates proliferation, invasion and apoptosis of endometrial cancer cells by recruiting p300/E2F1 in DLX6 promoter region. Journal of cellular and molecular medicine 23 32951317
2006 Dlx5- and Dlx6-mediated chondrogenesis: Differential domain requirements for a conserved function. Mechanisms of development 23 17027239
2023 Long non-coding RNA DLX6-AS1 is the key mediator of glomerular podocyte injury and albuminuria in diabetic nephropathy by targeting the miR-346/GSK-3β signaling pathway. Cell death & disease 22 36854759
2020 DLX6 Antisense RNA 1 Modulates Glucose Metabolism and Cell Growth in Gastric Cancer by Targeting microRNA-4290. Digestive diseases and sciences 22 32239379
2018 Long non-coding RNA DLX6-AS1 is upregulated in preeclampsia and modulates migration and invasion of trophoblasts through the miR-376c/GADD45A axis. Experimental cell research 22 30055134
2020 lncRNA DLX6-AS1 Promotes Proliferation of Laryngeal Cancer Cells by Targeting the miR-26a/TRPC3 Pathway. Cancer management and research 21 32368147
2014 Absent expression of the osteoblast-specific maternally imprinted genes, DLX5 and DLX6, causes split hand/split foot malformation type I. Journal of medical genetics 21 25332435
2020 LncRNA DLX6-AS1 Promotes the Progression of Neuroblastoma by Activating STAT2 via Targeting miR-506-3p. Cancer management and research 20 32904436
2020 Upregulated lncRNA DLX6-AS1 underpins hepatocellular carcinoma progression via the miR-513c/Cul4A/ANXA10 axis. Cancer gene therapy 20 33277615
2019 Long non-coding RNA DLX6-AS1 silencing inhibits malignant phenotypes of gastric cancer cells. Experimental and therapeutic medicine 20 31105791
2016 A Novel Heterozygous Intragenic Sequence Variant in DLX6 Probably Underlies First Case of Autosomal Dominant Split-Hand/Foot Malformation Type 1. Molecular syndromology 20 28611547
2009 Dlx5 Is a cell autonomous regulator of chondrocyte hypertrophy in mice and functionally substitutes for Dlx6 during endochondral ossification. PloS one 20 19956613
2020 Protective effect of DLX6-AS1 silencing against cerebral ischemia/reperfusion induced impairments. Aging 19 33216728
2021 DLX6-AS1 activated by H3K4me1 enhanced secondary cisplatin resistance of lung squamous cell carcinoma through modulating miR-181a-5p/miR-382-5p/CELF1 axis. Scientific reports 18 34697393
2019 LncRNA DLX6-AS1 promotes laryngeal squamous cell carcinoma growth and invasion through regulating miR-376c. American journal of translational research 18 31814904
2022 LncRNA DLX6-AS1 promotes microglial inflammatory response in Parkinson's disease by regulating the miR-223-3p/NRP1 axis. Behavioural brain research 17 35550840
2020 The regulatory network of lncRNA DLX6-AS1/miR-149-5p/ERP44 is possibly related to the progression of preeclampsia. Placenta 17 32250737
2018 Long non‑coding RNA DLX6‑AS1 promotes proliferation by acting as a ceRNA targeting miR‑199a in cervical cancer. Molecular medicine reports 17 30535431
2018 Long non‑coding RNA DLX6‑AS1 is associated with malignant progression and promotes proliferation and invasion in esophageal squamous cell carcinoma. Molecular medicine reports 17 30592268
2013 Endothelin regulates neural crest deployment and fate to form great vessels through Dlx5/Dlx6-independent mechanisms. Mechanisms of development 17 23933587
2012 Rapp-Hodgkin syndrome and SHFM1 patients: delineating the p63-Dlx5/Dlx6 pathway. Gene 17 22342398
2011 Allelic reduction of Dlx5 and Dlx6 results in early follicular depletion: a new mouse model of primary ovarian insufficiency. Human molecular genetics 17 21505076
2022 A Peptide Encoded by a Long Non-Coding RNA DLX6-AS1 Facilitates Cell Proliferation, Migration, and Invasion by Activating the wnt/β-Catenin Signaling Pathway in Non-Small-Cell Lung Cancer Cell. Critical reviews in eukaryotic gene expression 16 36017915
2020 RETRACTED: Long non-coding RNA DLX6-AS1 regulates neuroblastoma progression by targeting YAP1 via miR-497-5p. Life sciences 16 32289431
2020 LncRNA DLX6-AS1 Promotes Malignant Phenotype and Lymph Node Metastasis in Prostate Cancer by Inducing LARGE Methylation. Frontiers in oncology 16 32850336
2021 Silencing long non-coding RNA DLX6-AS1 or restoring microRNA-193b-3p enhances thyroid carcinoma cell autophagy and apoptosis via depressing HOXA1. Journal of cellular and molecular medicine 15 34514705
2020 Crosstalk between long non-coding RNA DLX6-AS1, microRNAs and signaling pathways: A pivotal molecular mechanism in human cancers. Gene 15 33059027
2020 DLX6 promotes cell proliferation and survival in oral squamous cell carcinoma. Oral diseases 15 33215805
2019 Long non-coding RNA DLX6-AS1 acts as an oncogene by targeting miR-613 in ovarian cancer. European review for medical and pharmacological sciences 15 31378881
2015 The apical ectodermal ridge of the mouse model of ectrodactyly Dlx5;Dlx6-/- shows altered stratification and cell polarity, which are restored by exogenous Wnt5a ligand. Human molecular genetics 15 26685160
2020 Long Noncoding RNA DLX6-AS1 Regulates the Growth and Aggressiveness of Colorectal Cancer Cells Via Mediating the miR-26a/EZH2 Axis. Cancer biotherapy & radiopharmaceuticals 14 32379493
2020 Silencing of long non-coding RNA DLX6-AS1 weakens neuroblastoma progression by the miR-513c-5p/PLK4 axis. IUBMB life 14 33031637
2019 Long noncoding RNA DLX6-AS1 targets miR-124-3p/CDK4 to accelerate Ewing's sarcoma. American journal of translational research 14 31737208
2022 DLX6-AS1: A Long Non-coding RNA With Oncogenic Features. Frontiers in cell and developmental biology 13 35281110
2020 DLX6-AS1 accelerates cell proliferation through regulating miR-497-5p/SNCG pathway in prostate cancer. Environmental toxicology 13 33035382
2019 Knockdown of long noncoding RNA DLX6-AS1 inhibits cell proliferation and invasion of cervical cancer cells by downregulating FUS. European review for medical and pharmacological sciences 13 31539117
2001 The coding region of the human DLX6 gene contains a polymorphic CAG/CCG repeat. International journal of oncology 13 11351265
2023 DANCR promotes glioma cell autophagy and proliferation via the miR‑33b/DLX6/ATG7 axis. Oncology reports 12 36601767
2003 No association between single nucleotide polymorphisms in DLX6 and Piccolo genes at 7q21-q22 and autism. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 12 12707945
2023 lncRNA DLX6-AS1 Promotes Myocardial Ischemia-Reperfusion Injury through Mediating the miR-204-5p/FBXW7 Axis. Mediators of inflammation 11 36660176
2021 DLX6-AS1 is a potential biomarker and therapeutic target in cancer initiation and progression. Clinica chimica acta; international journal of clinical chemistry 11 33607068
2019 Long noncoding RNA DLX6-AS1 functions as a competing endogenous RNA for miR-577 to promote malignant development of colorectal cancer. European review for medical and pharmacological sciences 11 31115000
2011 Dlx5 and Dlx6 expression in the anterior neural fold is essential for patterning the dorsal nasal capsule. Development (Cambridge, England) 11 21270050
2023 The lncRNA DLX6-AS1/miR-16-5p axis regulates autophagy and apoptosis in non-small cell lung cancer: A Boolean model of cell death. Non-coding RNA research 10 37767112
2021 Long non-coding RNA DLX6-AS1 knockdown suppresses the tumorigenesis and progression of non-small cell lung cancer through microRNA-16-5p/BMI1 axis. Translational cancer research 10 35116677
2024 DLX6-AS1 regulates odonto/osteogenic differentiation in dental pulp cells under the control of BMP9 via the miR-128-3p/MAPK14 axis: A laboratory investigation. International endodontic journal 9 38973098
2021 DLX6-AS1: An Indispensable Cancer-related Long Non-coding RNA. Current pharmaceutical design 9 33121401
2020 Promising long noncoding RNA DLX6-AS1 in malignant tumors. American journal of translational research 9 33437353
2019 Dlx5 and Dlx6 can antagonize cell division at the G1/S checkpoint. BMC molecular and cell biology 8 31041891
2021 Research progress of DLX6-AS1 in human cancers. Human cell 7 34508305
2020 Upregulation of long noncoding RNA DLX6-AS1 promotes cell growth and metastasis in esophageal squamous cell carcinoma via targeting miR-577. European review for medical and pharmacological sciences 7 32096208
2019 Posterior axis formation requires Dlx5/Dlx6 expression at the neural plate border. PloS one 6 30889190
2019 Knockdown of long noncoding RNA DLX6-AS1 inhibits migration and invasion of thyroid cancer cells by upregulating UPF1. European review for medical and pharmacological sciences 6 31858555