Expression, regulation and roles of miR-26a and MEG3 in tongue squamous cell carcinoma

Int J Cancer. 2014 Nov 15;135(10):2282-93. doi: 10.1002/ijc.28667. Epub 2014 Jun 19.

Abstract

MicroRNA miR-26a and long noncoding RNA (lncRNA) MEG3 gene have been independently reported to be tumor suppressor genes in various cancers, but neither has been previously associated with tongue squamous cell carcinoma (TSCC). We report here that miR-26a and lncRNA MEG3 gene expression were both strongly reduced in TSCC compared with levels in matched nonmalignant tissues, and combined low expression levels of both miR-26a and MEG3 emerged as an independent prognostic factor for poor clinical outcome in TSCC patients. Assays in the human TSCC cell lines SCC-15 and CAL27 showed that miR-26a targets the DNA methyltransferase 3B transcript and that its inhibition may result in the upregulation of MEG3, providing a plausible link between the observed reduction of miR-26a and MEG3 in TSCC tissue. Furthermore, the overexpression of miR-26a or MEG3 in SCC-15 and CAL27 cells inhibited cell proliferation and cell cycle progression, and promoted cell apoptosis. Considering the poor prognostic outcomes associated with reduced miR-26a and MEG3, our findings imply that these factors likely play important antitumor effects in TSCC pathogenesis. Furthermore, they represent potential prognostic biomarkers for stratification of TSCC patients.

Keywords: DNMT3B; MEG3; lncRNA; miR-26a; squamous cell carcinoma.

MeSH terms

  • Apoptosis
  • Blotting, Western
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Cell Cycle
  • Cell Proliferation
  • Cells, Cultured
  • DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methylation
  • DNA Methyltransferase 3B
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Tongue Neoplasms / genetics*
  • Tongue Neoplasms / mortality
  • Tongue Neoplasms / pathology

Substances

  • MEG3 non-coding RNA, human
  • MIRN26A microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger
  • DNA (Cytosine-5-)-Methyltransferases