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The miR-199a-5p/HIF1α dual-regulatory axis participates in hypoxia-induced aggressive phenotypes of oral squamous cell carcinoma (OSCC) cells.
- Source :
-
International journal of clinical oncology [Int J Clin Oncol] 2024 Sep; Vol. 29 (9), pp. 1244-1254. Date of Electronic Publication: 2024 Jun 09. - Publication Year :
- 2024
-
Abstract
- Background: The late-stage diagnosis and distant metastasis of oral squamous cell carcinoma (OSCC) remain a huge challenge to clinical treatment for OSCC. During the past decades, targeting glycolysis-inducing factors becomes an attractive new strategy in OSCC therapies.<br />Methods: OSCC cells were stimulated with hypoxia or transfected with agomir-199a-5p, antagomir-199a-5p, and siRNA for HIF1A, cell proliferation was detected by CCK-8 assay; HIF1α, GLUT1, HK2 and LDHA expression levels were examined with western blot; miR-199 expression was determined with RT-PCR; cell migratory and invasive abilities were examined using wound healing and transwell assays; the lactate and glucose in culture medium were also determined. Luciferase assay or CHIP assay was applied for confirm the binding between miR-199a-5p and HIF1A 3'UTR, or between HIF1α and miR-199a promoter.<br />Results: HIF1α showed to be abnormally up-regulated, and miR-199a-5p showed to be abnormally down-regulated within OSCC under hypoxia. Hypoxia considerably enhanced OSCC cell proliferation, glycolysis, migratory ability, and invasive ability. MiR-199a-5p bound to HIF1A 3'-UTR and suppressed HIF1A expression; HIF1α targeted miR-199a-5p promoter region and downregulated miR-199a-5p expression. Under hypoxia, miR-199a-5p overexpression significantly repressed HIF1α up-regulation inresponse to hypoxia, OSCC cell proliferation, glycolysis, migratory ability, and invasive ability.<br />Conclusion: miR-199a-5p and HIF1α form a dual-regulatory axis in OSCC cells; the miR-199a-5p/HIF1α dual-regulatory axis contributes to hypoxia-induced aggressive OSCC phenotypes.<br /> (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)
- Subjects :
- Humans
Cell Line, Tumor
Glycolysis genetics
Cell Hypoxia genetics
Neoplasm Invasiveness genetics
Phenotype
MicroRNAs genetics
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Hypoxia-Inducible Factor 1, alpha Subunit genetics
Mouth Neoplasms pathology
Mouth Neoplasms genetics
Mouth Neoplasms metabolism
Carcinoma, Squamous Cell genetics
Carcinoma, Squamous Cell pathology
Carcinoma, Squamous Cell metabolism
Cell Proliferation genetics
Gene Expression Regulation, Neoplastic
Cell Movement genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1437-7772
- Volume :
- 29
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- International journal of clinical oncology
- Publication Type :
- Academic Journal
- Accession number :
- 38853186
- Full Text :
- https://doi.org/10.1007/s10147-024-02555-7