MicroRNA-449a is downregulated in non-small cell lung cancer and inhibits migration and invasion by targeting c-Met

• Published in: PloS one 2013-05, Vol.8 (5), p.e64759-e64759
• Main Authors: Luo, Wenting, Huang, Bo, Li, Zixuan, Li, Haiying, Sun, Limei, Zhang, Qingfu, Qiu, Xueshan, Wang, Enhua
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; Adult; Aged; Apoptosis; Base Sequence; Biology; Biotechnology; Blotting, Western; Cancer; Cancer therapies; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell cycle; Cell Line; Cell migration; Cell Movement - genetics; Cell survival; Down-Regulation; Female; Fluorescence; Gene expression; Gene Expression Regulation, Neoplastic; Genomics; Growth factors; Humans; Kaplan-Meier Estimate; Low level; Lung cancer; Lung diseases; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lymph nodes; Lymphatic Metastasis; Male; Medical prognosis; Medicine; Metastases; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miRNA; Neoplasm Invasiveness; Non-small cell lung carcinoma; Pathology; Prognosis; Proportional Hazards Models; Proto-Oncogene Proteins c-met - genetics; Proto-Oncogene Proteins c-met - metabolism; Reverse Transcriptase Polymerase Chain Reaction - statistics & numerical data; Ribonucleic acid; RNA; Senescence; Stem cells; Target recognition; Tissues; Tumor cell lines; Tumor suppressor genes; Tumors; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0064759

MicroRNA-449a is expressed at a low level in several tumors and cancer cell lines, and induces G1 arrest, apoptosis, and senescence. To identify the function of miR-449a in non-small cell lung cancer (NSCLC), we discussed the potential relevance of miR-449a to clinicopathological characteristics and prognosis in NSCLC. We also investigated the impact of miR-449a on migration and invasion in NSCLC cells. The expression of miR-449a in NSCLC tissues and cell lines was detected using RT-qPCR. In vitro, gain-of-function, loss-of-function experiments, and fluorescence assays were performed to identify the potential target of miR-449a and the function of miR-449a in NSCLC cells. MiR-449a was downregulated in both NSCLC tissues and cell lines. Moreover, a low expression level of miR-449a appeared to be correlated with lymph node metastasis and poor survival. In vitro, miR-449 regulated cell migration and invasion in NSCLC cells as a potential tumor suppressor, at least in part by targeting c-Met. Furthermore, reciprocal expression of miR-449a and c-Met was shown in NSCLC tissue samples. This study indicates that miR-449a might be associated with NSCLC progression, and suggests a crucial role for miR-449a in NSCLC.