miR-186 regulation of Twist1 and ovarian cancer sensitivity to cisplatin

Abstract

Epithelial-mesenchymal transition (EMT) has an established role in promoting tumor progression and the acquisition of therapeutic resistance. Here, the EMT phenotype was detected in cisplatin-resistant ovarian cancer tissues and cell lines, and correlated with decreased miR-186 expression, increased Twist1 expression, chemoresistance and poor prognosis in epithelial ovarian cancer (EOC) patients. Introducing miR-186 into EOC cells led to a reduction in twist family bHLH transcription factor 1 (Twist1) expression along with morphological, functional and molecular changes consistent with mesenchymal-to-epithelial transition, G1 cell-cycle arrest and enhanced cell apoptosis, which consequently rendered the cells more sensitive to cisplatin in vitro and in vivo. Furthermore, luciferase reporter and rescue assay results showed that the EMT and drug resistance reversal in response to miR-186 was mediated by Twist1. Collectively, these findings implicate miR-186 as an attractive candidate for overcoming chemoresistance in ovarian cancer therapy.

Regulation of Collagen V Expression and Epithelial-Mesenchymal Transition by miR-185 and miR-186 during Idiopathic Pulmonary Fibrosis

“…This possibility is supported by previous reports of miR-185 and miR-186 inhibiting EMTrelated transcription factors STIM1 and TWIST1, respectively. 23,24 Our data suggest that treatment strategies using miR-185 and miR-186 mimics may take effect through Col(V)-dependent and Col(V)-independent mechanisms.…”

Curcumin inhibits cancer progression through regulating expression of microRNAs

“…82 Moreover, Twist1 (twist family bHLH transcription factor 1) and ABCB1 genes (ATP-binding cassette, sub-family B (MDR/TAP), member 1) were reported to be targeted by miR-186 which may account for overcoming chemoresistance of cisplatin in epithelial ovarian cancer. 83,84 Another research reported that curcumin suppressed the growth of resistant colon cancer cells treated with 5-FU and oxaliplatin through downregulating miR-21 and restoring PTEN levels with subsequent reduction in Akt phosphorylation. 85 In addition, further study revealed that the anti-cancer viability of the chemotherapeutic drug 5-FU in colon cancer was enhanced by curcumin due to the suppression of miR-27a.…”

MicroRNA-186 and metastatic prostate cancer.

“…We assessed whether 377 miRNAs were differentially expressed comparing non-cancerous controls to PCa patients with non-metastatic and bone-specific metastatic disease using Taqman There is a lot of controversy surrounding the role of miR-186 in relation to tumorigenesis. Six published studies suggest miR-186 has tumor suppressing potential; where as other studies indicate an oncogenic role [106][107][108][109][110][111][112]. Six other studies propose miR-186 has oncogenic potential.…”

“…Additionally in cervical cancer cells, miR-186 overexpression down-regulated the gene expression of pro-apoptotic gene, P2X7 [101]. However, the role of miR-186 in cancer may be tumor specific because it appears to have a tumor suppressor role in other cancers [106][107][108][109][110][111][112]. In the next chapter of this dissertation, we demonstrate inhibition of miR-186 corresponds with a suppression of cellular proliferation, anchorage independent growth and cellular invasion suggest miR-186 exhibits an oncogenic role in PCa within our metastatic PCa cell models.…”

“…Interestingly, the suppression of three different cancer hallmarks (i.e., proliferation, invasion and anchorage independent growth) was primarily MiR-186 has been implicated as a tumor suppressor in oral squamous, non-small cell lung, colorectal and ovarian cancer [106][107][108][109][110][111][112]. However, miR-186 has also been linked to an oncogenic role in several malignancies as well [63, 99-104, 106-108, 140, 141].…”