Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba, Japan.
Int J Mol Med. 2011 Mar;27(3):345-52. doi: 10.3892/ijmm.2010.589. Epub 2010 Dec 22.
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.
谷胱甘肽 S-转移酶 P1（GSTP1）蛋白在正常和肿瘤细胞中发挥着多种关键作用，包括 II 相异生物代谢、应激反应、信号转导和细胞凋亡。在许多类型的癌症中，包括头颈部鳞状细胞癌（HNSCC），都观察到 GSTP1 的过表达。然而，GSTP1 在 HNSCC 中的作用尚不清楚。我们研究了 GSTP1 在两种 HNSCC 细胞系 HSC3 和 SAS 中的作用。沉默 GSTP1 显示，两种细胞系中的癌细胞增殖均显著降低。此外，si-GSTP1 转染 HSC3 和 SAS 细胞系后，凋亡细胞的频率增加。越来越多的证据表明，微小 RNA（miRNA）负调控基因表达，并可在人类癌症中作为癌基因或肿瘤抑制因子发挥作用。基于基于网络搜索的结果，miR-133α 是 GSTP1 的候选 miRNA。miR-133α 在许多类型的人类癌症中下调，包括 HNSCC。miR-133α 的瞬时转染在 mRNA 和蛋白质水平上均抑制 GSTP1 的表达。GSTP1 3'UTR 上一个 miR-133α 靶位点的荧光素酶报告基因信号显著降低，表明 miR-133α 直接调节 GSTP1。我们的数据表明，GSTP1 可能具有致癌功能，并且可能受 miR-133α 调节，miR-133α 是 HNSCC 中的肿瘤抑制 miRNA。鉴定新的致癌途径可以为潜在的 HNSCC 致癌机制提供新的见解。
