miR-203 inhibits cell proliferation and promotes cisplatin induced cell death in tongue squamous cancer

Biochem Biophys Res Commun. 2016 Apr 29;473(2):382-7. doi: 10.1016/j.bbrc.2016.02.105. Epub 2016 Mar 3.

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most common types of the head and neck cancer. Chemo resistance of OSCC has been identified as a substantial therapeutic hurdle. In this study, we analyzed the role of miR-203 in the OSCC and its effects on cisplatin-induced cell death in an OSCC cell line, Tca8113. There was a significant decrease of miR-203 expression in OSCC samples, compared with the adjacent normal, non-cancerous tissue. After 3 days cisplatin treatment, the survived Tca8113 cells had a lower expression of miR-203 than that in the untreated control group. In contrast, PIK3CA showed an inverse expression in cancer and cisplatin survived Tca8113 cells. Transfection of Tca8113 cells with miR-203 mimics greatly reduced PIK3CA expression and Akt activation. Furthermore, miR-203 repressed PIK3CA expression through targeting the 3'UTR. Restoration of miR-203 not only suppressed cell proliferation, but also sensitized cells to cisplatin induced cell apoptosis. This effect was absent in cells that were simultaneously treated with PIK3CA RNAi. In summary, these findings suggest miR-203 plays an important role in cisplatin resistance in OSCC, and furthermore delivery of miR-203 analogs may serve as an adjuvant therapy for OSCC.

Keywords: Cell death; Cell proliferation; PI3KCA; Tongue squamous-cancer; miR-203.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Death / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology*
  • Class I Phosphatidylinositol 3-Kinases
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Signal Transduction / drug effects
  • Tongue / drug effects
  • Tongue / metabolism
  • Tongue / pathology
  • Tongue Neoplasms / drug therapy*
  • Tongue Neoplasms / genetics
  • Tongue Neoplasms / metabolism
  • Tongue Neoplasms / pathology

Substances

  • 3' Untranslated Regions
  • Antineoplastic Agents
  • MIRN203 microRNA, human
  • MicroRNAs
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • Cisplatin