To investigate miR-31 regulation on the metabolism and progression of oral cancer by targeting SIRT3

• Main Authors: Yu-Yu Kao, 高鈺祐
• Other Authors: Kuo-Wei Chang
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/398htg

博士 === 國立陽明大學 === 口腔生物研究所 === 105 === Background: Oral squamous cell carcinoma (OSCC) is one of the leading causes of cancer death in Taiwan, and it occurs more frequently in male population due to the abuse of tobacco and betel quid. To develop biomarkers for early cancer detection may bestow substantial benefits in diagnosis and the prevention of tumor progression. miRNAs are short, non-coding RNAs, which play important roles in oncogenesis. This study investigated the disruptions in miR-31, which could be associated with metabolic change and tumor progression. Methods: Mice were fed with 4-Nitroquinoline 1-Oxide (4NQO) in drinking water for 12 weeks and were kept for extended periods for tumor induction. The seahorse machine was used to detect the metabolic states of OSCC cell lines. The SIRT3 gene as potential miR-31 target to affect metabolism and tumor progression was also explored. Results: The histological and miR-31 level in body fluid evaluation showed the consecutive increase in the severity of epithelial pathogenesis from hyperkeratosis, hyperplasia to epithelial dysplasia and squamous tumors following the increase of 4NQO exposure. The increase of miR-31 staining parallels the severity of epithelial pathogenesis in tongue tissue. In addition, the expression of miR-31 target, SIRT3, was declined. SIRT3 expression is down-regulated in human OSCC. SIRT3 drives suppressor activity. miR-31-SIRT3 regulates the mitochondrial membrane potential and mitochondrial structure. miR-31 switched OSCC cell lines from aerobic metabolism to anaerobic metabolism. Conclusion: The disruption in the expression of oncogenic miRNAs in thus mouse model is similar to the disruption being identified in human oral cancer counterparts. miR-31-SIRT3 regulated the mitochondrial dysfunction and shift of the metabolism status in OSCC cell lines and worsened the tumor progression. As miR-31 was functionally oncogenic, the blockage of miR-31 expression would be valuable for the prevention of OSCC development.