title: Glutathione S-transferase P1 (GSTP1) suppresses cell apoptosis and its regulation by miR-133α in head and neck squamous cell carcinoma (HNSCC).
abstract: The glutathione S-transferase P1 (GSTP1) protein plays several critical roles in both normal and neoplastic cells, including phase II xenobiotic metabolism, stress responses, signaling and apoptosis. Overexpression of GSTP1 has been observed in many types of cancer, including head and neck squamous cell carcinoma (HNSCC). However, the role of GSTP1 in HNSCC is not well understood. We investigated the role of GSTP1 in two HNSCC cell lines, HSC3 and SAS. Silencing of GSTP1 revealed that cancer cell proliferation was significantly decreased in both cell lines. In addition, the frequency of apoptotic cells increased following si-GSTP1 transfection of HSC3 and SAS cell lines. Growing evidence suggests that microRNAs (miRNAs) negatively regulate gene expression and can function as oncogenes or tumor suppressors in human cancer. Based on the results of web-based searches, miR-133α is a candidate miRNA targeting GSTP1. Down-regulation of miR-133α has been reported in many types of human cancer, including HNSCC. Transient transfection of miR-133α repressed the expression of GSTP1 at both the mRNA and protein levels. The signal from a luciferase reporter was significantly decreased at one miR-133α target site at the 3'UTR of GSTP1, suggesting that miR-133α directly regulates GSTP1. Our data indicate that GSTP1 may have an oncogenic function and may be regulated by miR-133α, a tumor suppressive miRNA in HNSCC. The identification of a novel oncogenic pathway could provide new insights into potential mechanisms of HNSCC carcinogenesis.
authors.affiliation: Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Muradil
authors.initials: M
authors.lastname: Mutallip
authors.forename: Nijiro
authors.initials: N
authors.lastname: Nohata
authors.forename: Toyoyuki
authors.initials: T
authors.lastname: Hanazawa
authors.forename: Naoko
authors.initials: N
authors.lastname: Kikkawa
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Horiguchi
authors.forename: Lisa
authors.initials: L
authors.lastname: Fujimura
authors.forename: Kazumori
authors.initials: K
authors.lastname: Kawakami
authors.forename: Takeshi
authors.initials: T
authors.lastname: Chiyomaru
authors.forename: Hideki
authors.initials: H
authors.lastname: Enokida
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D051549:Glutathione S-Transferase pi / Q000096:biosynthesis*; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D012334:RNA, Neoplasm / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi