ArticleInternational journal of molecular sciences2020
Hypoxia-Induced miR-675-5p Supports β-Catenin Nuclear Localization by Regulating GSK3-β Activity in Colorectal Cancer Cell Lines.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- miRNA675-5p inhibitor's dual role as novel therapeutic alternative or sensitizing treatment in resistant glioma models.Molecular therapy. Nucleic acids · 2026Article
- Recent advances in novel targeting mechanisms for colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Nuclear-Cytoplasmic Axis in Cancer: From Protein Mislocalization to Anticancer Drug Resistance.Oncology research · 2026Review
- Regulatory role of lncH19 in RAC1 alternative splicing: implication for RAC1B expression in colorectal cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Decreased expression of H19/miR-675 ameliorates hypoxia-induced oxaliplatin resistance in colorectal cancer.Heliyon · 2024Article
- Regulation of Cancer-Associated miRNAs Expression under Hypoxic Conditions.Analytical cellular pathology (Amsterdam) · 2024Review
- P53‑microRNA interactions regulate the response of colorectal tumor cells to oxaliplatin under normoxic and hypoxic conditions.Oncology reports · 2023Article
- Structural Modifications and Novel Protein-Binding Sites in Pre-miR-675-Explaining Its Regulatory Mechanism in Carcinogenesis.Non-coding RNA · 2023Article
- Long non-coding RNA H19 enhances the pro-apoptotic activity of ITF2357 (a histone deacetylase inhibitor) in colorectal cancer cells.Frontiers in pharmacology · 2023Article
- Article
- Glycogen synthase kinase GSK3α promotes tumorigenesis by activating HIF1/VEGFA signaling pathway in NSCLC tumor.Cell communication and signaling : CCS · 2022Article
- MicroRNAs Are Key Molecules Involved in the Gene Regulation Network of Colorectal Cancer.Frontiers in cell and developmental biology · 2022Review
- Rapamycin-Loaded Polymeric Nanoparticles as an Advanced Formulation for Macrophage Targeting in Atherosclerosis.Pharmaceutics · 2021Article
- Hypoxia-Induced Non-Coding RNAs Controlling Cell Viability in Cancer.International journal of molecular sciences · 2021Review
- Article
- An updated review of the H19 lncRNA in human cancer: molecular mechanism and diagnostic and therapeutic importance.Molecular biology reports · 2020Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The reduction of oxygen partial pressure in growing tumors triggers numerous survival strategies driven by the transcription factor complex HIF1 (Hypoxia Inducible Factor-1). Recent evidence revealed that HIF1 promotes rapid and effective phenotypic changes through the induction of non-coding RNAs, whose contribution has not yet been fully described. Here we investigated the role of the hypoxia-induced, long non-coding RNA H19 (lncH19) and its intragenic miRNA (miR-675-5p) into HIF1-Wnt crosstalk. During hypoxic stimulation, colorectal cancer cell lines up-regulated the levels of both the lncH19 and its intragenic miR-675-5p. Loss of expression experiments revealed that miR-675-5p inhibition, in hypoxic cells, hampered β-catenin nuclear localization and its transcriptional activity, while lncH19 silencing did not induce the same effects. Interestingly, our data revealed that miRNA inhibition in hypoxic cells restored the activity of Glycogen Synthase Kinase 3β (GSK-3β) reducing the amount of P-Ser9 kinase, thus unveiling a role of the miR-675-5p in controlling GSK-3β activity. Bioinformatics analyses highlighted the serine/threonine-protein phosphatases PPP2CA, responsible for GSK-3β activation, among the miR-675-5p targets, thus indicating the molecular mediator through which miR-675-5p may control β-catenin nuclear localization. In conclusion, here we demonstrated that the inhibition of the hypoxia-induced non-coding RNA miR-675-5p hampered the nuclear localization of β-catenin by regulating GSK-3β activity, thus proposing the miR-675-5p as a new therapeutic target for the treatment of colorectal cancer.
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Registered trials
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 OpenQuestion graph.