MiR-497 decreases cisplatin resistance in ovarian cancer cells by targeting mTOR/P70S6K1

Abstract

The mechanism of cisplatin resistance in ovarian cancer is not clearly understood. In the present investigation, we found that the expression levels of miR-497 were reduced in chemotherapy-resistant ovarian cancer cells and tumor tissues due to hypermethylation of miR-497 promoter. Low miR-497 expression levels were associated with chemo-resistant phonotype of ovarian cancer. By analyzing the expression levels of miR-497, mTOR and p70S6K1 in a clinical gene-expression array dataset, we found that mTOR and p70S6K1, two proteins correlated to chemotherapyresistance in multiple types of human cancers, were inversely correlated with miR-497 levels in ovarian cancer tissues. By using an orthotopic ovarian tumor model and a Tet-On inducible miR-497 expression system, our results demonstrated that overexpression of miR-497 sensitizes the resistant ovarian tumor to cisplatin treatment. Therefore, we suggest that miR-497 might be used as a therapeutic supplement to increase ovarian cancer treatment response to cisplatin.

Inhibition of Mir-128-3p by Tongxinluo Protects Human Cardiomyocytes From Ischemia/Reperfusion Injury via Upregulation of P70s6k1/P-P70s6k1

“…Our study demonstrated that TXL promoted p70s6k1 expression without changing p70s6k1 mRNA levels, leading us to investigate the role of microRNAs in the anti-apoptotic effects of TXL. Among the three microRNAs (Shi et al, 2012;Xu et al, 2012Xu et al, , 2015) previously reported to target p70s6k1 mRNA and inhibit its translation, only miR-128-3p was downregulated by TXL during I/R. MiR-128-3p was implicated as important in multiple physiological and pathophysiological processes, such as angiogenesis, neuronal plasticity, cholesterol metabolism and differentiation Adlakha and Saini, 2014).…”

“…Because TXL was reported to decrease expression of microRNAs and increase levels of their corresponding proteins under certain conditions (Wang J .Y. et al, 2014;Zhang et al, 2014Zhang et al, , 2017, we used quantitative PCR to examine levels of several microRNAs (Shi et al, 2012;Xu et al, 2012Xu et al, , 2015 The effects of TXL on the protein levels of total p70s6k1 and phosphorylated p70s6k1 in myocardium (n = 4 in each group). *P < 0.05 vs. Sham; # P < 0.05 vs. I/R; $ P < 0.05 vs. I/R+TXL; Ra, rapamycin; TA, total cross-sectional heart area; AAR, area at risk; IA, infract area.…”

Cardamonin enhances the anti-proliferative effect of cisplatin on ovarian cancer

“…It was reported that the phosphorylation level of mTOR was higher in cisplatin-insensitive clear-cell ovarian carcinoma cells compared with in cisplatin-sensitive cells (12,13). mTOR also performs a key role in the modulation of cisplatin-induced apoptotic cell death.…”

miR‐495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression

“…reported that miRNAs are involved in the regulation of chemoresistance to ovarian cancer, colorectal cancer, non‐small cell lung cancer or breast cancer by targeting mTOR/P70S6K1 and MAP/ERK kinase kinase 1 (MEKK1), among others. In addition, using the targeting miRNAs, they resensitized drug‐resistant cells to anticancer agents .…”