MiR-125b inhibits tumor growth and promotes apoptosis of cervical cancer cells by targeting phosphoinositide 3-kinase catalytic subunit delta

Cell Physiol Biochem. 2012;30(5):1310-8. doi: 10.1159/000343320. Epub 2012 Oct 22.

Abstract

Background: [corrected] microRNAs (miRNAs) are involved in cancer-related processes. The miRNA-125b (miR-125b) has been identified as miRNA over-expressed in a wide variety of cancers. However, the role of miR-125b in the context of cervical carcinoma remains unknown.

Methods: In this study, the effect of miR-125b on the proliferation and apoptosis of human cervical cells was analyzed by MTT assay and Flow cytometry analysis. we identified phosphoinositide 3-kinase catalytic subunit delta (PIK3CD) as a novel miR-125b target.

Results: overexpression of miR- 125b in HeLa cervical cancer cells decreased cell proliferation, induced apoptosis and down-regulated expression of PIK3CD. To identify the mechanisms responsible, we investigated the PI3K/Akt pathway and found that PI3K, phospho-Akt, and phospho-mTOR were all down-regulated, while Bid was up-regulated in miR-125b-overexpressing subclones. In vivo, over expression of miR-125b in HeLa cells markedly reduced their ability to form tumors.

Conclusion: these results suggest that miR-125b suppresses tumor growth activity by targeting the PI3K/ Akt/mTOR signaling pathway, and may provide a target for effective therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents*
  • Apoptosis*
  • Cell Proliferation
  • Class I Phosphatidylinositol 3-Kinases
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • HeLa Cells
  • Humans
  • MicroRNAs / genetics*
  • Phosphatidylinositol 3-Kinases / biosynthesis
  • Phosphatidylinositol 3-Kinases / genetics*
  • Structure-Activity Relationship
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology*

Substances

  • Antineoplastic Agents
  • MIRN125 microRNA, human
  • MicroRNAs
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CD protein, human