Expression of microRNA-338 in lung adenocarcinoma and its inhibition mechanism of lung cancer metastasis

Abstract

Objective To study the expression of microRNA (miRNA, miR)-338 in lung adenocarcinoma cell line and lung adenocarcinoma tissues, and to study the mechanism of lung cancer metastasis. Methods The expression of miR-338 was detected by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) in lung adenocarcinoma cell line A549, and 115 cases of lung adenocarcinoma tissues and normal lung tissues adjacent to tumor. To construct miR-338 over expressing lung cancer cell line and explore the function of miR-338 in the proliferation, invasion and metastasis of lung cancer cells. To detect the expression of integrin β3 in miR-338 over expression lung cancer cell line, and to study the mechanism of miR-338 inhibiting lung cancer metastasis. Results (1)The expression of miR-338 was down regulated in lung adenocarcinoma cell line and lung adenocarcinoma tissues (1.00 vs. 0.15±0.01, P=0.035), (0.00 vs. -2.99±3.69, P=0.001). The expression of miR-338 was correlated with tumor embolus, tumor recurrence, TNM stage (P=0.005, 0.004, 0.025). The 5 years overall survival rate of the low expression group was significantly lower than that of the high expression group (median survival time 44 months vs. 53 months, P=0.001). (2) Up-regulating the expression of miR-338 can inhibit the proliferation of lung cancer cells, migration [average cell count (347±41) cells vs. (190±8) cells, P=0.029] and invasion [average cell count (197±12) cells vs. (68±14) cells, P=0.008]. Xenograft tumor model in nude mice showed that the high expression of miR-338 can effectively inhibit the growth of transplanted tumor [average tumor clone number (20±7) cells vs. (4±2) cells, P=0.004]. (3) In the miR-338 over expression lung adenocarcinoma cell line, the expression of integrin β3 was significantly lower than that in control cells (1.00 vs. 0.35±0.04, P=0.001). Dual luciferase activity assay revealed that the miR-338 over expression group was reduced in the luciferase activity (1.00 vs. 0.75±0.08, P=0.030). Conclusion (1) MiR-338 can inhibit the proliferation, invasion and metastasis of lung cancer cells; (2) MiR-338 play a negative regulation post transcription by targeting the integrin β3 3’untranslated regions (3’UTR) mRNA region. integrin β3 is a new miR-338 lung cancer target gene. Key words: Lung adenocarcinoma; Metastasis; MicroRNA-338; Integrin β3