MiR-454 promotes the progression of human non-small cell lung cancer and directly targets PTEN

• Published in: Biomedicine & pharmacotherapy 2016-07, Vol.81, p.79-85
• Main Authors: Zhu, Deng-Yan, Li, Xiang-Nan, Qi, Yu, Liu, Dong-Lei, Yang, Yang, Zhao, Jia, Zhang, Chun-Yang, Wu, Kai, Zhao, Song
• Format: Article
• Language: English
• Subjects: Apoptosis; Base Sequence; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Humans; Internal Medicine; Kaplan-Meier Estimate; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medical Education; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; MiR-454; Multivariate Analysis; Non-small cell lung cancer; Prognosis; Proliferation; PTEN; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2016.03.029

Abstract Purpose MicroRNA-454 has been proven dysregulated in some human malignancies and correlated with tumor progression. However, its expression and function in non-small cell lung cancer (NSCLC) is still unclear. Thus, the aim of this study was to explore the effects of miR-454 in NSCLC tumorigenesis and development. Methods Using quantitative RT-PCR, we detected miR-454 expression in NSCLC cell lines and primary tumor tissues. The association of miR-454 expression with clinicopathological factors and prognosis was also analyzed. Then, the effects of miR-454 on the biological behavior of NSCLC cells were investigated. At last, the potential regulatory function of miR-454 on PTEN expression was confirmed. Results miR-454 was found to be up-regulated in NSCLC tissues and cell lines. High miR-454 expression was closely correlated with lymph node metastasis, advanced TNM stage, and shorter overall survival. Multivariate regression analysis corroborated that miR-454 overexpression was an independent unfavourable prognostic factor for patients with NSCLC. Down-regulation of miR-454 could significantly reduce NSCLC cell proliferation, enhance cell apoptosis, and impair cell invasion and migration in vitro, while up-regulation of miR-454 showed opposite effects. Further, PTEN was confirmed as a direct target of miR-454 by using Luciferase Reporter Assay. Conclusions These findings indicate that miR-454 may act as an oncogene in NSCLC and would serve as a potential therapy target for this disease.