MicroRNA-129-5p inhibits invasiveness and metastasis of lung cancer cells and tumor angiogenesis via targeting VEGF

X.-K. Cheng, W.-R. Lin, H. Jiang, Z.-H. Su, L. Li, J. Wang

Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. wangjignsdu@163.com

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• Oncology

OBJECTIVE: This study was to find out the influence of microRNA-129-5p on proliferative ability, invasiveness, and metastasis of lung tumor cells and tumor angiogenesis. Besides, the effects of microRNA-129-5p on vascular endothelial growth factor (VEGF) level and potential regulatory mechanisms were also what we were interested in.
PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay was performed to detect the microRNA-129-5p level in tumor tissues and paracancerous tissues of 50 patients with LCa, and the interaction between microRNA-129-5p expression and LCa pathological parameters was analyzed. The untreated cell group (NC) and the transfected microRNA-129-5p overexpression group (microRNA-129-5p mimics) were established, and then, the transfection efficiency of microRNA-129-5p was further verified by qRT-PCR. In H1299 and SPC-A1, cell counting kit-8 (CCK-8), Tube-formation experiments, and transwell invasion and migration tests were performed to evaluate the influence of the microRNA on the biological function of LCa cells. Finally, the potential mechanism of action of VEGF, a downstream gene of microRNA-129-5p, was explored by bioinformatics analysis and recovery experiments.
RESULTS: QRT-PCR results showed that the level of microRNA-129-5p in cancer tissues of LCa patients was notably lower than that in normal tissues, and the difference was statistically significant. Compared with patients with highly expressed microRNA-129-5p, patients with low level had higher rates of lymph node or distant metastasis, and the overall survival rate was lower. Compared with NC group, cell proliferation, invasiveness and migration ability, and tumor angiogenesis capacity were strikingly decreased in microRNA-129-5p mimics group. Subsequently, VEGF expression was validated conspicuously enhanced in LCa cell line and tissue and was negatively correlated with microRNA-129-5p. In addition, the recovery experiment demonstrated that overexpression of VEGF could counteract the impact of microRNA-129-5p mimics on tumor angiogenesis and the invasive and migratory capacity of LCa cells, which then together led to the malignant progression of LCa.
CONCLUSIONS: The above studies demonstrated that microRNA-129-5p was strikingly correlated with LCa lymph node or distant metastasis and poor prognosis, and it can inhibit the malignant progression of this cancer. The investigation also demonstrated that microRNA-129-5p may inhibit proliferation capacity and invasiveness of LCa cells and tumor angiogenesis via regulating VEGF.

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