RRC ID 45249
Author Konno Y, Dong P, Xiong Y, Suzuki F, Lu J, Cai M, Watari H, Mitamura T, Hosaka M, Hanley SJ, Kudo M, Sakuragi N.
Title MicroRNA-101 targets EZH2, MCL-1 and FOS to suppress proliferation, invasion and stem cell-like phenotype of aggressive endometrial cancer cells.
Journal Oncotarget
Abstract MicroRNA-101 has been implicated as a tumor suppressor miRNA in human tumors. However, its potential functional impact and the underlying mechanisms in endometrial cancer progression have not been determined. Here, we report that in aggressive endometrial cancer cells, re-expression of microRNA-101 leads to inhibition of cell proliferation and induction of apoptosis and senescence. Ectopic overexpression of microRNA-101 attenuates the epithelial-mesenchymal transition-associated cancer cell migration and invasion, abrogates the sphere-forming capacity and enhances chemosensitivity to paclitaxel. Algorithm and microarray-based strategies identifies potential microRNA-101 targets. Among these, we validated EZH2, MCL-1 and FOS as direct targets of miR-101 and silencing of these genes mimics the tumor suppressive effects observed on promoting microRNA-101 function. Importantly, further results suggest an inverse correlation between low miR-101 and high EZH2, MCL-1 and FOS expression in EC specimens. We conclude that, as a crucial tumor suppressor, microRNA-101 suppresses cell proliferation, invasiveness and self-renewal in aggressive endometrial cancer cells via modulating multiple critical oncogenes. The microRNA-101-EZH2/MCL-1/FOS axis is a potential therapeutic target for endometrial cancer.
Volume 5(15)
Pages 6049-62
Published 2014-8-15
DOI 10.18632/oncotarget.2157
PII 2157
PMID 25153722
PMC PMC4171612
MeSH Cell Growth Processes / genetics Cell Movement / genetics Endometrial Neoplasms / genetics* Endometrial Neoplasms / pathology Enhancer of Zeste Homolog 2 Protein Female Humans MicroRNAs / genetics MicroRNAs / metabolism* Myeloid Cell Leukemia Sequence 1 Protein / genetics Myeloid Cell Leukemia Sequence 1 Protein / metabolism* Neoplasm Invasiveness Oncogene Proteins v-fos / genetics Oncogene Proteins v-fos / metabolism* Phenotype Polycomb Repressive Complex 2 / genetics Polycomb Repressive Complex 2 / metabolism*
IF 5.168
Times Cited 56
Human and Animal Cells