MALAT1 promotes osteosarcoma development by targeting TGFA via MIR376A

Oncotarget. 2016 Aug 23;7(34):54733-54743. doi: 10.18632/oncotarget.10752.

Abstract

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that contributes to the initiation and development of many solid tumors, including osteosarcoma (OS). Here, we showed that MALAT1 was increased in human OS cell lines and tissues and promoted OS cell growth, while MALAT1 knockdown suppressed OS cell growth. We also detected downregulation of MIR376A, a suppressor of OS growth, and upregulation of TGFA, a promoter of OS growth, in OS tissues. TGFA expression was positively correlated with MALAT1 expression, and both were negatively correlated with MIR376A expression. There was a direct interaction between MIR376A and MALAT1 via a putative MIR376A binding site within the MALAT1 3'-untranslated region (3'-UTR). There was also a direct interaction between MIR376A and the TGFA 3'-UTR. Thus, MALAT1 may promote OS cell growth through inhibition of MIR376A, leading to increased expression of TGFA. Our results suggest a MALAT1/MIR376A/TGFA axis mediates OS cell proliferation and tumor progression.

Keywords: IncRNA; MALAT1; MIR376A; TGFA; osteosarcoma.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Disease Progression
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics*
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology
  • RNA, Long Noncoding / genetics*
  • Transforming Growth Factor alpha / genetics*
  • Transforming Growth Factor alpha / metabolism

Substances

  • 3' Untranslated Regions
  • MALAT1 long non-coding RNA, human
  • MIRN376C microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • TGFA protein, human
  • Transforming Growth Factor alpha