ArticleCancers2023
miR-34a and IRE1A/XBP-1(S) Form a Double-Negative Feedback Loop to Regulate Hypoxia-Induced EMT, Metastasis, Chemo-Resistance and Autophagy.
Article in Cancers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- The p53-Associated Regulation of ATF4 mRNA Expression Involves p21 and p130 in a Stress-Dependent Manner.Cells · 2026Article
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- Myeloid Mir34a suppresses initiation and progression of intestinal and colitis-induced colon cancers in APCCell death & disease · 2026Article
- A Novel Prognostic Signature Composed of Autophagy and Liver Metastasis in Colorectal Cancer: Comprehensive Analysis of Bulk and Single-Cell Transcriptomic Data.ImmunoTargets and therapy · 2026Article
- Endoplasmic Reticulum Stress: Triggers Microenvironmental Regulation and Drives Tumor Evolution.Cancer medicine · 2025Review
- Review
- Hypoxia-Inducible Factor-Dependent and Independent Mechanisms Underlying Chemoresistance of Hypoxic Cancer Cells.Cancers · 2024Review
- The dual role of autophagy in the regulation of cancer treatment.Amino acids · 2024Review
- CRISPR/Cas9-mediated inactivation of miR-34a and miR-34b/c in HCT116 colorectal cancer cells: comprehensive characterization after exposure to 5-FU reveals EMT and autophagy as key processes regulated by miR-34.Cell death and differentiation · 2023Article
- Regulatory miRNAs in cancer cell recovery from therapy exposure and its implications as a novel therapeutic strategy for preventing disease recurrence.The Enzymes · 2023Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Tumor-associated hypoxia, i.e., decreased availability of oxygen, results in a poor clinical outcome since it promotes EMT, metastasis, and chemotherapy-resistance. We have previously identified p53 and its target miR-34a, as critical determinants of the effect of hypoxia on colorectal cancer (CRC). Here, we aimed to characterize mechanisms that contribute to the selective advantage of cells with loss of p53/miR-34a function in a hypoxic environment. Using in silico prediction, we identified XBP-1 and IRE1A as potential miR-34a targets. IRE1A and XBP-1 are central components of the unfolded protein response that is activated by ER stress, which is also induced in tumor cells as a response to harsh conditions surrounding tumors such as hypoxia and a limited supply of nutrients. Here we characterized the XBP-1(S) transcription factor and its regulator IRE1A as direct, conserved miR-34a targets in CRC cells. After hypoxia and DNA damage, IRE1A and XBP-1 were repressed by p53 in a miR-34a-dependent manner, whereas
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