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.

• Authors: X Zhu, H Shen, X Yin, L Long, C Xie, Y Liu, L Hui, X Lin, Y Fang, Y Cao, Y Xu, M Li, W Xu, Y Li
• Journal: Oncogene (Oncogene) Vol. 35 Issue 3 Pg. 323-32 (Jan 21 2016) ISSN: 1476-5594 [Electronic] England
• PMID: 25867064 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN186 microRNA, human
• MicroRNAs
• Nuclear Proteins
• TWIST1 protein, human
• Twist-Related Protein 1
• Cisplatin

Topics

• Adult
• Aged
• Animals
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cisplatin (administration & dosage)
• Drug Resistance, Neoplasm (genetics)
• Epithelial-Mesenchymal Transition (genetics)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Mice
• MicroRNAs (biosynthesis, genetics)
• Middle Aged
• Neoplasm Staging
• Nuclear Proteins (biosynthesis, genetics)
• Ovarian Neoplasms (drug therapy, genetics, pathology)
• Twist-Related Protein 1 (biosynthesis, genetics)
• Xenograft Model Antitumor Assays