MIR-19A PARTICIPATES IN PROLIFERATION AND METASTASIS OF NON-SMALL CELL LUNG CANCER CELLS BY REGULATING SMAD4

Guifei Yu, Xiaobo Yu, Xi Chen, Qiang Lin^* 

Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China

Objective: This study was designed to probe into the miR-19a expression in non-small cell lung cancer (NSCLC), and to discuss its function and molecular mechanism. 

Methods: Thirty-five cases of NSCLC and corresponding normal lung tissues were collected, and the miR-19a relative expression was tested via qRT-PCR. miR-19a-inhibitor, miR-NC and sh-Smad4 were transfected into A549 cells. The miR-19a and Smad4 expression levels were tested by qRT-PCR. Proliferation changes of cells after transfection were assessed by CCK8 test. Cell migration and apoptosis were tested via flow cytometry. The relationship between miR-27a and Smad4 was confirmed via dual-luciferase report. The expression changes of caspase-3 and caspase-9 in transfected cells were detected via Western Blot (WB). 

Results: The miR-19a expression in NSCLC tissues was obviously higher than that in normal tissues, while the Smad4 expression in lung cancer (LC) tissues was remarkably lower than that in normal ones (P<0.05). Proliferation, migration and invasion of A549 cells were dramatically inhibited and apoptosis was promoted after being transfected with miR-19a-inhibitor. While cell proliferation, migration and invasion were remarkably accelerated and apoptosis was inhibited after being transfected with sh-Smad4. miR-19a was confirmed as a Smad4 target site via dual-luciferase report. 

Conclusion: The miR-19a expression is up-regulated in NSCLC tissues, which may advance cell proliferation and metastasis by down-regulating the Smad4 expression.