Upregulation of miR-192 inhibits cell growth and invasion and induces cell apoptosis by targeting TCF7 in human osteosarcoma

Tumour Biol. 2016 Nov;37(11):15211-15220. doi: 10.1007/s13277-016-5417-z. Epub 2016 Sep 28.

Abstract

MicroRNAs (miRNAs) can function as oncogenes or tumor suppressor genes and are involved in multiple processes in cancer development and progression. For example, miR-192 is dysregulated in multiple human cancers, including osteosarcoma (OS). However, the pathophysiological role of miR-192 and its relevance to OS cell growth and invasion has not yet been clarified. This study aimed to investigate the expression of miR-192 in OS and elucidate the molecular mechanisms by which miR-192 acts as a tumor suppressor in this disease. The qRT-PCR data identified significant down-regulation of miR-192 in 20 OS tissue samples and two OS cell lines when compared with adjacent normal tissues and a human osteoblast cell line, respectively. Furthermore, Western blot analysis revealed overexpression of T cell-specific transcription factor (TCF) 7 protein in tumor tissues compared with matched adjacent normal tissues. Further in vitro studies demonstrated that enforced expression of miR-192 inhibited U2OS and MG63 cell proliferation, invasion, and migration and induced apoptosis. Finally, Western blot and Luciferase assays identified TCF7 as a target of miR-192. Collectively, these findings suggest an important role for miR-192 in regulating the proliferation, migration, invasion, and apoptosis of OS cells through the regulation of TCF7.

Keywords: Apoptosis; Invasion; Osteosarcoma; Proliferation; TCF7; miR-192.

Publication types

  • Comparative Study

MeSH terms

  • Apoptosis
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology*
  • Bone and Bones / metabolism
  • Bone and Bones / pathology
  • Case-Control Studies
  • Cell Movement*
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • T Cell Transcription Factor 1 / genetics
  • T Cell Transcription Factor 1 / metabolism*
  • Tumor Cells, Cultured

Substances

  • MIRN192 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • T Cell Transcription Factor 1
  • TCF7 protein, human