| 2015 |
IRX1 promotes osteosarcoma metastasis by upregulating CXCL14/NF-κB signaling; experimental modulation of IRX1 in osteosarcoma cell lines altered migration, invasion, and resistance to anoikis in vitro, and lung metastasis in murine models, with effects mediated through CXCL14/NF-κB pathway activation. |
MeDIP-microarray screening, IRX1 overexpression/knockdown in cell lines, in vitro migration/invasion/anoikis assays, murine lung metastasis models |
The Journal of clinical investigation |
High |
25822025
|
| 2010 |
IRX1 functions as a tumor suppressor in gastric cancer; its expression is silenced by promoter hypermethylation (not mutation), and restoring IRX1 expression inhibits growth, invasion, and tumorigenesis. Direct IRX1 target genes identified by ChIP assay include BDKRB2, HIST2H2BE, and FGF7. |
5-Aza-dC treatment, IRX1 transfection, global microarray, real-time PCR, chromatin immunoprecipitation (ChIP), in vitro and in vivo tumorigenesis assays |
Oncogene |
High |
20440264
|
| 2011 |
IRX1 suppresses peritoneal spreading and pulmonary metastasis in gastric cancer via inhibition of angiogenesis and vasculogenic mimicry (VM), mechanistically through downregulation of its direct target BDKRB2 and its downstream effector PAK1; siRNA knockdown of BDKRB2 or PAK1 inhibited tube formation, proliferation, migration, and invasion. |
IRX1 transfection, siRNA knockdown of BDKRB2/PAK1, HUVEC angiogenesis assays, chick embryo assay, VM formation assay, in vivo murine metastasis models |
Oncogene |
High |
21602894
|
| 2018 |
PRMT5 acts as an upstream epigenetic repressor of IRX1 in gastric cancer by recruiting DNMT3A to the IRX1 promoter, increasing promoter methylation and silencing IRX1 expression; Co-IP confirmed PRMT5-DNMT3A interaction and ChIP confirmed DNMT3A recruitment to the IRX1 promoter. |
Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), PRMT5 overexpression/knockdown, methylation analysis, in vitro and in vivo tumorigenicity assays |
Biochimica et biophysica acta. Molecular basis of disease |
High |
29802960
|
| 2017 |
Irx1 null mice are neonatal lethal due to pulmonary immaturity; Irx1 marks alveolar type II cells and is required for surfactant protein secretion. In dental development, Irx1 is expressed in outer enamel epithelium and mediates dental epithelial cell differentiation. Mechanistically, Irx1 regulates Foxj1 and Sox9 to control cell differentiation. |
Irx1 LacZ knock-in null mice, histology, LacZ lineage tracing, lung and dental phenotype analysis, target gene expression analysis (Foxj1, Sox9) |
Developmental biology |
Medium |
28746823
|
| 2016 |
IRX1 binds to the MLL-AF4 complex at target gene promoters and counteracts its promoter-activating function in t(4;11) leukemia cells; IRX1 also induces transcription of HOXB4 and EGR family members. |
ChIP at target gene promoters, gene expression analysis, HDACi perturbation experiments in t(4;11) leukemia cell lines |
Oncotarget |
Medium |
27175594
|
| 2021 |
miR-646 targets TET1, reducing TET1-mediated demethylation of the IRX1 promoter, which suppresses IRX1 expression; reduced IRX1 leads to upregulation of HIST2H2BE, promoting invasive ductal carcinoma progression. ChIP confirmed TET1 enrichment at the IRX1 promoter. |
miR-646 gain/loss-of-function, methylation-specific PCR, ChIP for TET1 at IRX1 promoter, RT-qPCR, Western blot, in vitro and in vivo functional assays |
Genomics |
Medium |
33667646
|
| 2018 |
IRX1 activates KLF1 and TAL1 transcription in megakaryocyte-erythroid progenitors (MEPs); knockdown and stimulation experiments in AML cell lines confirmed these as IRX1 target genes, implicating IRX1 in normal myeloid differentiation at the MEP stage. |
RNA-seq expression profiling, IRX1 knockdown and stimulation experiments in AML cell lines (megakaryoblastic and myelomonocytic), comparative gene expression analysis |
International journal of molecular sciences |
Medium |
35328612
|
| 2025 |
IRX1 is expressed in gingival epithelial basal stem cell niches and is required for oral wound healing; mechanistically, IRX1 activates SOX9 in the transient amplifying layer to increase cell proliferation and activates EGF signaling to induce cell migration. Irx1+/- heterozygous mice show delayed wound closure and defective keratinocyte proliferation/differentiation. |
Irx1+/- heterozygous mice, RNA-seq (WT vs Irx1+/-), Krt14CreERT lineage tracing, wound healing assays, immunofluorescence, gene expression analysis |
JCI insight |
Medium |
39782692
|
| 2013 |
HNF1B controls IRX1/2 expression during nephron segmentation; HNF1B is recruited to regulatory sequences of IRX1/2 and their downregulation (alongside Notch pathway components) accompanies failure of proximal-intermediate nephron segment fate acquisition upon Hnf1b conditional inactivation. |
Hnf1b conditional knockout in murine nephron progenitors, ChIP (HNF1B binding to IRX1/2 regulatory regions), Xenopus dominant-negative overexpression, in situ hybridization |
Development (Cambridge, England) |
Medium |
23362348
|
| 2018 |
Six1 and Irx1 reciprocally regulate each other during cranial placode and otic vesicle formation in Xenopus; Six1 expands then represses Irx1 expression, while Irx1 initially expands then represses Six1; Irx1 and Sox11 (a direct Six1 target) also reciprocally regulate each other. |
Xenopus ectodermal explants, microarray screen, gain- and loss-of-function experiments, in situ hybridization, temporal expression analysis |
Developmental biology |
Medium |
30529252
|
| 2022 |
DNA methylation of the IRX1/2 locus in undifferentiated hiPSCs correlates with neural differentiation propensity; forced expression of IRX1/2 impaired neural differentiation ability of hiPSCs, demonstrating a functional role for IRX1 expression levels in determining neural stem cell fate. |
Infinium MethylationEPIC BeadChip (32 hiPSC lines), HSIC Lasso feature selection, IRX1/2 forced expression, neural differentiation efficiency assay |
Regenerative therapy |
Medium |
36514370
|
| 2026 |
IRX1 suppresses breast cancer progression by inhibiting de novo fatty acid synthesis; mechanistically, IRX1 interacts with NME1 (confirmed by Co-IP), promotes NME1 nuclear localization, and the IRX1-NME1 complex transcriptionally downregulates ACACA (acetyl-CoA carboxylase alpha), reducing fatty acid synthesis. |
Co-immunoprecipitation (IRX1-NME1 interaction), nuclear localization assays, IRX1 overexpression/knockdown, ACACA expression analysis, de novo fatty acid synthesis assays, in vitro and in vivo tumor models |
Cell death & disease |
Medium |
42225620
|
| 2019 |
IRX1 hypermethylation in heart failure suppresses CXCL14 expression; demethylation with 5-aza-2'-deoxycytidine restored IRX1 and CXCL14 expression and alleviated heart failure in a transverse aortic constriction (TAC) rat model. |
TAC rat model, 5-Aza treatment, Western blot, qRT-PCR, cardiac ultrasound, immunofluorescence, bioinformatic analysis |
Cell cycle (Georgetown, Tex.) |
Low |
31640472
|
| 2019 |
miR-150 negatively regulates IRX1 expression in gastric cancer; miR-150 inhibition or IRX1 overexpression restricted proliferation, migration, and invasion while promoting apoptosis, with CXCL14 and NF-κB (p65) expression negatively correlated with IRX1 levels. |
miR-150 gain/loss-of-function, IRX1 overexpression/silencing, cell proliferation, colony formation, migration/invasion, apoptosis assays, in vivo xenograft |
IUBMB life |
Low |
31846199
|
| 2025 |
Irx1 is expressed in M3, M4, and M5 ipRGC subtypes downstream of Tbr2; Irx1 ablation reduces Opn4 (melanopsin) expression specifically in M3, M4, and M5 ipRGCs without affecting the formation of Irx1-expressing ipRGCs, placing Irx1 in a Tbr2-dependent transcription cascade controlling ipRGC subtype fate and Opn4 expression. |
Irx1 conditional ablation in retinal development, Opn4 expression analysis by immunofluorescence/RNA, ipRGC subtype characterization |
bioRxivpreprint |
Low |
bio_10.1101_2025.04.29.651262
|