Let-7c inhibits A549 cell proliferation through oncogenic TRIB2 related factors

• Published in: FEBS letters 2013-08, Vol.587 (16), p.2675-2681
• Main Authors: Wang, Ping-Yu, Sun, Yun-Xiao, Zhang, Shuai, Pang, Min, Zhang, Han-Han, Gao, Shu-Yan, Zhang, Can, Lv, Chang-Jun, Xie, Shu-Yang
• Format: Article
• Language: English
• Subjects: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; Animals; antisense oligonucleotides; Apoptosis; ASO; C/EBP; Calcium-Calmodulin-Dependent Protein Kinases; CCAAT-Enhancer-Binding Protein-alpha - metabolism; CCAAT/enhancer-binding protein; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Gene expression; Gene Expression Regulation, Neoplastic; Genetic Vectors; Green Fluorescent Proteins - metabolism; HCC; hepatocellular carcinoma; Humans; Intracellular Signaling Peptides and Proteins - metabolism; Let-7c; Lung adenocarcinoma; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; MAPK; Mice; Mice, Nude; microRNAs; MicroRNAs - metabolism; miRNAs; mitogen-activated protein kinase; MTT; Neoplasm Transplantation; Oligonucleotides, Antisense - metabolism; p38 Mitogen-Activated Protein Kinases - metabolism; TRIB2 gene
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2013.07.004

•Let-7c inhibits lung adenocarcinoma cell proliferation in vitro and in vivo.•Let-7c is a tumor suppressor miRNA to induce A549 cell apoptosis.•The tumor suppressive role of let-7c is relevant to regulating cell cycle.•Oncogene TRIB2 is a new target of let-7c.•Let-7c can regulate TRIB2-related C/EBP-α and phosphorylated p38MAPK. MicroRNAs have tumor suppressive or oncogenic roles in carcinogenesis. This study aimed to investigate the mechanism of let-7c in suppressing lung cancer cell proliferation. First, let-7c was revealed to be able to inhibit lung adenocarcinoma cell proliferation significantly. TRIB2 was further demonstrated to be a novel target and negatively regulated by let-7c. As downstream signals of TRIB2, the activities of C/EBP-α and phosphorylated p38MAPK were increased obviously in let-7c-treated cells compared with controls. Our results demonstrate that, through regulating the expression of TRIB2 and its downstream factors, let-7c can effectively inhibit A549 cell proliferation in vitro and in vivo.