Journal
CANCER LETTERS
Volume 456, Issue -, Pages 40-48Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2019.04.028
Keywords
Carcinoma; miRNA; miR-31; Mitochondria; Oral; SIRT3
Categories
Funding
- Ministry of Science and Technology [102-2628-B-010-011-MY3, 103-2314-B-010-020-MY3]
- Ministry of Health and Welfare, Taiwan [MOHW108-TDU-B-211-124019]
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MicroRNA miR-31 is implicated in the neoplastic process of various malignancies including oral squamous cell carcinoma (OSCC). Silent information regulator 3 (Sirtuin3 or SIRT3) is a NAD-dependent deacetylase that regulates metabolic process. Suppressor role of SIRT3 has been found in neoplasms. This study investigates the disruptions of miR-31-SIRT3 cascade to explore their potential association with metabolic change in OSCC. We identified that miR-31 directly targeted SIRT3 in OSCC cells, and a reverse correlation between miR-31 expression and SIRT3 expression was noted in OSCC tumors. SIRT3 expression attenuated the miR-31 enhanced tumor cell migration and invasion. It also reduced the tumorigenic potential of FaDu cell line. miR-31-SIRT3 impaired the mitochondrial membrane potential and structural integrity. The dis-regulation of this axis also contributed to the genesis of oxidative stress. In addition, miR-31 switched tumor cells from aerobic metabolism to glycolytic metabolism. This study provides novel evidences demonstrating the presence of miR-31-mediated post-transcriptional regulation of SIRT3 in OSCC. The disruption of miR-31-SIRT3 cascade and the consequential metabolic aberrances are involved in OSCC progression.
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