To Investigate the Effect of 1α,25-Dihydroxyvitamin D3 Regulating MiR-93-5p on Prostate Cancer Cells

• Main Authors: ZENG, BO-SHENG, 曾柏盛
• Other Authors: TING, HUEI-JU
• Format: Others
• Language: zh-TW
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/evrbsw

碩士 === 國立臺南大學 === 生物科技學系碩士班 === 107 === Prostate cancer (PCa) is one of the most common cancers in men and its survival rate after metastasis is much lower, therefore the molecular mechanisms for cancer metastasis are crucial therapeutic targets. Collective evidence prove the signal transduction of vitamin D are important for combating PCa. Our laboratory recently reported that active form vitamin D, 1α,25-dihydroxyvitamin D3 (1,25-VD), will inhibit the expression of miR-93-5p, an oncomir, in PCa cell line. Here we further investigate the effects of miR-93-5p inhibitor (anti-miR93) and 1,25-VD on the behavior of an aggressive PCa cell line, PC-3, using both in vitro and in vivo xenograft mouse model. The results showed that 1,25-VD but not anti-miR93 inhibited cell growth. The similar result was observed in tumor growth of PC-3 xenograft mice model. The inhibitive effects of anti-miR93 or 1,25-VD alone on PC-3 migration were 70% and 30 %, respectively. The fact that combined treatment did not show additive effect suggests that miR-93-5p mediates the anti-migratory effect of 1,25-VD. The anti-angiogenesis effect of 1,25-VD and anti-miR93 were examined in the tumors of PC-3 xenograft mice model. The preliminary results showed that 1,25-VD, but not anti-miR93, inhibited angiogenesis. Next, we explore the downstream target genes of miR-93-5p, especially those involved in cell migration, by in-silico analysis and literature search. One of candidate genes, TCF21, were confirmed to be upregulated by anti-miR93 and 1,25-VD treatment. Overall, these results revealed that 1,25-VD significantly downregulated miR-93-5p which mediates the inhibitory effect of 1,25-VD on cell migration. In the future, we will investigate the regulatory mechanism and the role of miR-93-5p inhibiting TCF21 in controlling PCa progression.