Evidence mapPaperPMID 42284709Full record

ArticleTranslational oncology2026

HIF1-driven TDP-43 stabilizes TRIP6 mRNA to drive angiogenesis and colorectal cancer progression under hypoxia.

Ke Cheng, Yonggang Liu, Weiyu Feng, Dongli Xu, Bin Hao

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Article in Translational oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Ke ChengThe Second Clinical College of Zhengzhou University, No. 127, Dongming Road, Jinshui District, Zhengzhou 450003, China.
Yonggang LiuThe Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450003, China.
Weiyu FengThe Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450003, China.
Dongli XuThe Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450003, China.
Bin HaoThe Second Clinical College of Zhengzhou University, No. 127, Dongming Road, Jinshui District, Zhengzhou 450003, China. Electronic address: binhao688@126.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hypoxia is a key feature of the tumor microenvironment in colorectal cancer (CRC), but the mechanisms linking hypoxia to metastasis remain incompletely understood. To investigate this, bioinformatics analysis of The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) datasets assessed TAR DNA-binding protein 43 (TDP-43) expression and its correlation with hypoxia-inducible factor-1α (HIF1A). In vitro and in vivo functional assays, including Cell Counting Kit-8 (CCK-8), Transwell, chicken chorioallantoic membrane (CAM), and xenograft, were conducted to evaluate proliferation, migration, invasion, and angiogenesis. Mechanistic studies, including chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), luciferase reporter, and actinomycin D assay, were conducted to elucidate HIF1-mediated transcriptional regulation of TARDBP and TDP-43-dependent stabilization of thyroid receptor-interacting protein 6 (TRIP6) mRNA. As a result, TDP-43 was upregulated in CRC tissues and correlated with HIF1A expression. Hypoxia induced TDP-43 expression through HIF1-dependent transcriptional activation via direct binding to hypoxia-response element (HRE) 3 site in the TARDBP promoter. TARDBP knockdown suppressed hypoxia-induced proliferation, migration, invasion, and vascular endothelial growth factor (VEGF) secretion, which were rescued by HIF1A overexpression. RIP-qPCR revealed TDP-43 binding to TRIP6 mRNA via its RNA recognition motifs (RRM domains), stabilizing TRIP6 transcripts and promoting its expression. TRIP6 reconstitution reversed the anti-tumor effects of TARDBP silencing. In vivo, TARDBP depletion inhibited tumor growth and downregulated metastasis-related factors in xenograft models. In conclusion, the HIF1-TARDBP-TRIP6 axis promotes CRC malignancy under hypoxia by integrating transcriptional activation and post-transcriptional mRNA stabilization, offering potential therapeutic targets for advanced CRC.

Indexed as

AngiogenesisColorectal cancerHypoxiaTDP-43TRIP6

Identifiers

PMID42284709
PMCPMC13279019

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.