Downregulation of microRNA-34 induces cell proliferation and invasion of human mesothelial cells

Norimitsu Tanaka, Shinichi Toyooka, Junichi Sou, Kazunori Tsukuda, Kazuhiko Shien, Masashi Furukawa, Takayuki Muraoka, Yuho Maki, Tsuyoshi Ueno, Hiromasa Yamamoto, Hiroaki Asano, Takemi Otsuki, Shinichiro Miyoshi

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

Malignant mesothelioma (MM) is an aggressive tumor with a dismal prognosis, and the molecular alterations involved in this disease remain unknown. We previously reported that microRNA-34s (miR-34s) are methylated and downregulated in MM and may play an important role in the carcinogenesis of MM. In this study, we downregulated miR-34s in human mesothelial cells to investigate the cellular effect of miR-34 knockdown. For the cell study, we used LP-9, a human mesothelial cell line, and three human primary-cultured mesothelial cell lines. RNA-based miR-34a, -34b and -34c inhibitors were transfected into these cells, and their effects on proliferation and invasion were evaluated. A scramble RNA oligonucleotide was used as a control. The protein expression status was estimated using western blotting. After miR-34 inhibitor transfection, miR-34a, -34b and -34c were downregulated in all the examined mesothelial cell lines. miR-34 inhibitor transfection significantly increased cell proliferation in all of the mesothelial cell lines, compared with the scramble control. The invasive ability also increased in the miR-34 inhibitor transfectants, compared with the scramble control, in the LP-9 cell line. Western blotting confirmed the upregulation of c-MET, phospho-c-MET, and Bcl-2 proteins in LP-9 cells after miR-34 inhibitor transfection. In conclusion, our study showed that the downregulation of miR-34s induced an oncogenic phenotype in non-malignant mesothelial cells. The present study, together with the results of our previous report, strongly suggest that miR-34s play an important role in the early carcinogenic process involved in the transformation of human mesothelial cells to MM.

Original languageEnglish
Pages (from-to)2169-2174
Number of pages6
JournalOncology reports
Volume29
Issue number6
DOIs
Publication statusPublished - Jun 2013

Keywords

  • Carcinogenesis
  • Mesothelial cells
  • Mesothelioma
  • MicroRNA-34
  • Non-coding RNA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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