miR-138 inhibits proliferation by targeting 3-phosphoinositide-dependent protein kinase-1 in non-small cell lung cancer cells

• Published in: The clinical respiratory journal Vol. 9; no. 1; pp. 27 - 33
• Main Authors: Ye, Xian-wei, Yu, Hong, Jin, Yan-kun, Jing, Xiao-ting, Xu, Mei, Wan, Zi-fen, Zhang, Xiang-yan
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.01.2015; John Wiley & Sons, Inc
• Subjects: 3-phosphoinositide-dependent protein kinase-1; 3-Phosphoinositide-Dependent Protein Kinases - genetics; 3-Phosphoinositide-Dependent Protein Kinases - metabolism; Carcinoma, Non-Small-Cell Lung - enzymology; Carcinoma, Non-Small-Cell Lung - etiology; Carcinoma, Non-Small-Cell Lung - pathology; Cell Culture Techniques; Cell Line, Tumor; cell proliferation; Cell Proliferation - physiology; Humans; Kinases; Lung cancer; Lung Neoplasms - enzymology; Lung Neoplasms - etiology; Lung Neoplasms - pathology; MicroRNAs - physiology; miR-138; non-small cell lung cancer; Proteins; RNA, Messenger - metabolism; siRNA; non-small cell lung cancer; siRNA; miR-138; cell proliferation; 3-phosphoinositide-dependent protein kinase-1
• ISSN: 1752-6981; 1752-699X; 1752-699X
• DOI: 10.1111/crj.12100

Objective Underlying mechanisms of non‐small cell lung cancer (NSCLC) development remain poorly understood. miR‐138 and 3‐phosphoinositide‐dependent protein kinase‐1 (PDK1) have been reported to be involved in the genesis of NSCLC. The aim of this study was to investigate the role and mechanisms of miR‐138 and PDK1 in human NSCLC cells. Methods The effect of miR‐138 on proliferation of A549 lung cancer cells was first examined using 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide assay. The expression of PDK1 in A549 lung cancer cells was assessed by real‐time polymerase chain reaction further. A luciferase reporter activity assay was conducted to confirm target association between miR‐138 and 3′ untranslated region (3′‐UTR) of PDK1. Finally, the role of PDK1 on proliferation of A549 cells was evaluated by transefection of PDK1 small interfering RNA (siRNA). Results Proliferation of A549 lung cancer cells was suppressed by miR‐138 in a concentration‐dependent manner. Furthermore, miR‐138 can bind to the 3′‐UTR of PDK1 and downregulate expression of PDK1 at both mRNA and protein levels. Knockdown of PDK1 by siRNA significantly inhibits the proliferation of A549 lung cancer cells. Conclusions These findings suggest that miR‐138 as a potential tumor suppressor could inhibit cell proliferation by targeting PDK1 in NSCLC cells, which could be employed as a potential therapeutic target for miRNA‐based NSCLC therapy.