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

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

doi:10.3892/or.2013.2351

June 2013 Volume 29 Issue 6

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June 2013 Volume 29 Issue 6

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Article

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

Authors:
- Norimitsu Tanaka
- Shinichi Toyooka
- Junichi Soh
- Kazunori Tsukuda
- Kazuhiko Shien
- Masashi Furukawa
- Takayuki Muraoka
- Yuho Maki
- Tsuyoshi Ueno
- Hiromasa Yamamoto
- Hiroaki Asano
- Takemi Otsuki
- Shinichiro Miyoshi
View Affiliations / Copyright

Affiliations: Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan, Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
Pages: 2169-2174
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Published online on: March 19, 2013

https://doi.org/10.3892/or.2013.2351
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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.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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