Tumor suppressive microRNA-133a regulates novel molecular networks in lung squamous cell carcinoma

Yasumitsu Moriya, Nijiro Nohata, Takashi Kinoshita, Muradil Mutallip, Tatsuro Okamoto, Shigetoshi Yoshida, Makoto Suzuki, Ichiro Yoshino, Naohiko Seki

Research output: Contribution to journalArticle

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Abstract

Analysis of the microRNA (miRNA) expression signature of lung squamous cell carcinoma (lung-SCC) revealed that the expression levels of miR-133a were significantly reduced in cancer tissues compared with normal tissues. In this study, we focused on the functional significance of miR-133a in cancer cell lines derived from lung-SCC and the identification of miR-133a-regulated novel cancer networks in lung-SCC. Restoration of miR-133a expression in PC10 and H157 cell lines resulted in significant inhibition of cell proliferation, suggesting that miR-133a functions as a tumor suppressor. We used genome-wide gene expression analysis to identify the molecular targets of miR-133a regulation. Gene expression data and web-based searching revealed several candidate genes, including transgelin 2 (TAGLN2), actin-related protein2/3 complex, subunit 5, 16kDa (ARPC5), LAG1 homolog, ceramide synthase 2 (LASS2) and glutathione S-transferase pi 1 (GSTP1). ARPC5 and GSTP1 likely represent bona fide targets as their expression is elevated in lung-SCC clinical specimens. Furthermore, transient transfection of miR-133a, repressed ARPC5 and GSTP1 mRNA and protein levels. As cell proliferation was significantly inhibited in lung-SCC cells following RNAi knock down of either gene, ARPC5 and GSTP1 may function as oncogenes in the development of lung-SCC. The identification of a tumor suppressive miRNA and the novel cancer pathways it regulates could provide new insights into potential molecular mechanisms of lung-SCC carcinogenesis.

Original languageEnglish
Pages (from-to)38-45
Number of pages8
JournalJournal of Human Genetics
Volume57
Issue number1
DOIs
Publication statusPublished - Jan 1 2012

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MicroRNAs
Squamous Cell Carcinoma
Glutathione S-Transferase pi
Lung
Actins
Neoplasms
Cell Proliferation
Gene Knockdown Techniques
Gene Expression
Cell Line
RNA Interference
Oncogenes
Transfection
Carcinogenesis
Genome
Messenger RNA
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Moriya, Y., Nohata, N., Kinoshita, T., Mutallip, M., Okamoto, T., Yoshida, S., ... Seki, N. (2012). Tumor suppressive microRNA-133a regulates novel molecular networks in lung squamous cell carcinoma. Journal of Human Genetics, 57(1), 38-45. https://doi.org/10.1038/jhg.2011.126

Tumor suppressive microRNA-133a regulates novel molecular networks in lung squamous cell carcinoma. / Moriya, Yasumitsu; Nohata, Nijiro; Kinoshita, Takashi; Mutallip, Muradil; Okamoto, Tatsuro; Yoshida, Shigetoshi; Suzuki, Makoto; Yoshino, Ichiro; Seki, Naohiko.

In: Journal of Human Genetics, Vol. 57, No. 1, 01.01.2012, p. 38-45.

Research output: Contribution to journalArticle

Moriya, Y, Nohata, N, Kinoshita, T, Mutallip, M, Okamoto, T, Yoshida, S, Suzuki, M, Yoshino, I & Seki, N 2012, 'Tumor suppressive microRNA-133a regulates novel molecular networks in lung squamous cell carcinoma', Journal of Human Genetics, vol. 57, no. 1, pp. 38-45. https://doi.org/10.1038/jhg.2011.126
Moriya, Yasumitsu ; Nohata, Nijiro ; Kinoshita, Takashi ; Mutallip, Muradil ; Okamoto, Tatsuro ; Yoshida, Shigetoshi ; Suzuki, Makoto ; Yoshino, Ichiro ; Seki, Naohiko. / Tumor suppressive microRNA-133a regulates novel molecular networks in lung squamous cell carcinoma. In: Journal of Human Genetics. 2012 ; Vol. 57, No. 1. pp. 38-45.
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