Elevated MiR-222-3p promotes proliferation and invasion of endometrial carcinoma via targeting ERα

PLoS One. 2014 Jan 31;9(1):e87563. doi: 10.1371/journal.pone.0087563. eCollection 2014.

Abstract

MicroRNAs play key roles in tumor proliferation and invasion. Here we show distinct expression of miR-222-3p between ERα-positive and ERα-negative endometrial carcinoma (EC) cell lines and primary tumors, and investigation of its relationship with ERα and other clinical parameters. In vitro, the function of miR-222-3p was examined in RL95-2 and AN3CA cell lines. MiR-222-3p expression was negatively correlated with ERα. Over-expressed miR-222-3p in RL95-2 cells promoted cell proliferation, enhanced invasiveness and induced a G1 to S phase shift in cell cycle. Furthermore, the miR-222-3p inhibitor decreased the activity of AN3CA cells to proliferate and invade. In vivo, down-regulated miR-222-3p of AN3CA cells inhibited EC tumor growth in a mouse xenograft model. Additionally, miR-222-3p increased raloxifene resistance through suppressing ERα expression in EC cells. In conclusion, miR-222-3p plays a significant role in the regulation of ERα expression and could be potential targets for restoring ERα expression and responding to antiestrogen therapy in a subset of ECs.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cell Line, Tumor
  • Endometrial Neoplasms / metabolism*
  • Endometrial Neoplasms / pathology
  • Estrogen Receptor alpha / biosynthesis*
  • Estrogen Receptor alpha / genetics
  • Female
  • G1 Phase*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Mice
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • RNA, Neoplasm / biosynthesis*
  • RNA, Neoplasm / genetics
  • S Phase*

Substances

  • ESR1 protein, human
  • Estrogen Receptor alpha
  • MIRN222 microRNA, human
  • MIRN222 microRNA, mouse
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm

Grants and funding

This study was supported by Grants from the National Natural Science Funds of China (Nos. 81072139, 81172476 and 81272885). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.