title: Tumor suppressive microRNA-133a regulates novel molecular networks in lung squamous cell carcinoma.
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.
authors.affiliation: Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba, Japan.
authors.forename: Yasumitsu
authors.initials: Y
authors.lastname: Moriya
authors.forename: Nijiro
authors.initials: N
authors.lastname: Nohata
authors.forename: Takashi
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Muradil
authors.initials: M
authors.lastname: Mutallip
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Okamoto
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Yoshida
authors.forename: Makoto
authors.initials: M
authors.lastname: Suzuki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yoshino
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks / Q000235:genetics*; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D056726:Genetic Association Studies; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi