microRNA-199a is able to reverse cisplatin resistance in human ovarian cancer cells through the inhibition of mammalian target of rapamycin

Abstract

microRNAs (miRNAs/miRs) may have a crucial function in tumor metastasis through the regulation of a plethora of signaling pathways. Increasing evidence has shown that miR-199a is important in regulating the tumor metastasis of ovarian cancer, although the precise biological function of miR-199a is unclear at present. In the current study, it was observed that the expression levels of miR-199a were higher in OV2008 cells compared with C13* cells. However, lower levels of mammalian target of rapamycin (mTOR) protein were detected by western blotting in the OV2008 cells compared with the C13* cells. The miR-199a levels were increased in the C13* cells using miR-199a mimics and the mTOR levels were observed to decrease. This may have resulted in a reversal of cisplatin resistance in the C13* cells. To test this hypothesis, the Renilla luciferase reporter gene system was used to analyze the mTOR levels. The results indicated that the expression levels of mTOR were significantly blocked by the increased miR-199a levels. When the miR-199a inhibitor was applied to decrease the miR-199a levels, it was observed that the mTOR expression levels were increased, while cisplatin-induced apoptosis was decreased in the OV2008 cells. The study concludes that miR-199a is able to reverse cisplatin resistance in human ovarian cancer cells through the inhibition of mTOR and that mTOR may be the target of miR-199a during this process.

MiR‐199a/b‐3p suppresses migration and invasion of breast cancer cells by downregulating PAK4/MEK/ERK signaling pathway

“…A). Recent studies demonstrated that overexpression of miR‐199a/b‐3p suppressed proliferation, multidrug resistance, and migration in cancer cells with miR‐199a/b‐3p down‐regulated, such as in hepatocellular carcinoma , ovarian cancer , renal cell carcinoma , osteosarcoma , papillary thyroid carcinoma , and endometrioid adenocarcinoma . All of these phenomena demonstrated whether the decreased expression level of miR‐199a/b‐3p was associated with aggression of breast cancer.…”

The prognostic role of microRNA in epithelial ovarian cancer: a systematic review of literature with an overall survival meta-analysis

“…Cao and cols. (2014) concluded that patients with high expression of miR-200a, miR-200b, and mi-R200c present shorter overall survival than the corresponding controls (all p < 0.001) [21]. Moreover, Pal and cols.…”

miRNA Therapy Targeting Cancer Stem cells: a New Paradigm for Cancer Treatment and Prevention of Tumor Recurrence

“…Inhibition of invasion and metastasis [75] miR-888 Up E-cadherin Promotion of EMT [76] let-7 Down HRAS, HMGA2 Inhibition of self-renewal [77] miR-7 Down SETDB1 Inhibition of invasion and metastasis [78] miR-200c Down BMI-1, SUZ12 Inhibition of self-renewal [79] Colorectal cancer miR-21 Up TGFBR Modulation of Wnt signaling [80] miR-140 Up HDAC4, CXCL2 Chemosensitivity [81,82] miR-215 Up DTL Chemosensitivity [83] miR-34 Down NOTCH1 Suppression of asymmetric cell division [84] miR-93 Down HDAC8, TLE4 Inhibition of proliferation [85] miR-328 Down ABCG2 Inhibition of chemoresistance [86] miR-451 Down MIF, COX-2 Inhibition of self-renewal and tumorigenicity [87] miR-451 Down ABCB1 Inhibition of chemoresistance [87] Ovarian cancer miR-214 Up P53/NANOG Promotion of self-renewal [88] miR-199a Down CD44 Inhibition of proliferation and invasion [89] miR-199a Down mTOR Induction of chemoresistance of CD133+ cells [90] miR-200a Down ZEB2 Inhibition of migration and invasion [91] Prostate cancer miR-34 Down CD44…”

“…The inhibition of CD44 by miR-199a reduces expression of the multidrug resistance gene ABCG2 and thereby increases the chemosensitivity of ovarian CSCs [89]. In addition, miR-199a is also implicated in cisplatin resistance because inhibition of miR-199a increases mammalian target of rapamycin expression and decreases cisplatin-induced apoptosis in vitro [90].…”