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 language | English |
|---|---|
| Pages (from-to) | 38-45 |
| Number of pages | 8 |
| Journal | Journal of Human Genetics |
| Volume | 57 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 2012 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Genetics
- Genetics(clinical)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Tumor suppressive microRNA-133a regulates novel molecular networks in lung squamous cell carcinoma
AU - Moriya, Yasumitsu
AU - Nohata, Nijiro
AU - Kinoshita, Takashi
AU - Mutallip, Muradil
AU - Okamoto, Tatsuro
AU - Yoshida, Shigetoshi
AU - Suzuki, Makoto
AU - Yoshino, Ichiro
AU - Seki, Naohiko
PY - 2012/1/1
Y1 - 2012/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84863013767&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863013767&partnerID=8YFLogxK
U2 - 10.1038/jhg.2011.126
DO - 10.1038/jhg.2011.126
M3 - Article
C2 - 22089643
AN - SCOPUS:84863013767
VL - 57
SP - 38
EP - 45
JO - Journal of Human Genetics
JF - Journal of Human Genetics
SN - 1434-5161
IS - 1
ER -