Sawai, Sakunie and Wong, Pooi-Fong and Ramasamy, Thamil Selvee (2022) Hypoxia-regulated microRNAs: The molecular drivers of tumor progression. Critical Reviews in Biochemistry and Molecular Biology, 57 (4). pp. 351-376. ISSN 1040-9238, DOI https://doi.org/10.1080/10409238.2022.2088684.
Full text not available from this repository.Abstract
Hypoxia is a common feature of the tumor microenvironment (TME) of nearly all solid tumors, leading to therapeutic failure. The changes in stiffness of the extracellular matrix (ECM), pH gradients, and chemical balance that contribute to multiple cancer hallmarks are closely regulated by intratumoral oxygen tension via its primary mediators, hypoxia-inducible factors (HIFs). HIFs, especially HIF-1 alpha, influence these changes in the TME by regulating vital cancer-associated signaling pathways and cellular processes including MAPK/ERK, NF-kappa B, STAT3, PI3K/Akt, Wnt, p53, and glycolysis. Interestingly, research has revealed the involvement of epigenetic regulation by hypoxia-regulated microRNAs (HRMs) of downstream target genes involved in these signaling. Through literature search and analysis, we identified 48 HRMs that have a functional role in the regulation of 5 key cellular processes: proliferation, metabolism, survival, invasion and migration, and immunoregulation in various cancers in hypoxic condition. Among these HRMs, 17 were identified to be directly associated with HIFs which include miR-135b, miR-145, miR-155, miR-181a, miR-182, miR-210, miR-224, miR-301a, and miR-675-5p as oncomiRNAs, and miR-100-5p, miR-138, miR-138-5p, miR-153, miR-22, miR-338-3p, miR-519d-3p, and miR-548an as tumor suppressor miRNAs. These HRMs serve as a potential lead in the development of miRNA-based targeted therapy for advanced solid tumors. Future development of combined HIF-targeted and miRNA-targeted therapy is possible, which requires comprehensive profiling of HIFs-HRMs regulatory network, and improved formula of the delivery vehicles to enhance the therapeutic kinetics of the targeted cancer therapy (TCT) moving forward.
| Item Type: | Article |
|---|---|
| Funders: | Ministry of Higher Education, Malaysia through the Fundamental Research Grant Scheme [FRGS -FP028-2018A] [FRGS/1/2018/SKK08/UM/02/27] |
| Uncontrolled Keywords: | Hypoxia; MicroRNAs; Resistance; Tumor progression; Metabolic reprogramming; Cell survival; Cancer stem cells (CSCs); MiRNA-based targeted therapy |
| Subjects: | R Medicine |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 14 Sep 2023 04:20 |
| Last Modified: | 14 Sep 2023 04:20 |
| URI: | http://eprints.um.edu.my/id/eprint/41219 |
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