MicroRNA-101 targets EZH2, MCL-1 and FOS to suppress proliferation, invasion and stem cell-like phenotype of aggressive endometrial cancer cells

Yosuke Konno, Peixin Dong, Ying Xiong, Fumihiko Suzuki, Jiabin Lu, Muyan Cai, Hidemichi Watari, Takashi Mitamura, Masayoshi Hosaka, Sharon J.B. Hanley, Masataka Kudo, Noriaki Sakuragi

Research output: Contribution to journalArticlepeer-review

118 Citations (Scopus)

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 transitionassociated 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.

Original languageEnglish
Pages (from-to)6049-6062
Number of pages14
JournalOncotarget
Volume5
Issue number15
DOIs
Publication statusPublished - 2014

Keywords

  • EMT
  • EZH2
  • FOS
  • MCL-1
  • MicroRNA-101
  • Proliferation

ASJC Scopus subject areas

  • Oncology

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