MiRNA-621 inhibits the malignant progression of non-small cell lung cancer via targeting SIX4

M. Zhang, H. Shi, C. Zhang, S.-Q. Zhang

Department of Thoracic Surgery, Shengzhou Renmin Hospital, Shengzhou, China. zhangsq230@163.com

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• Oncology

OBJECTIVE: To clarify the role of microRNA-621 (miRNA-621)/SIX4 axis in regulating the malignant progression of non-small cell lung cancer (NSCLC) and the potential mechanism.
PATIENTS AND METHODS: MiRNA-621 expression in NSCLC tissues and paracancerous tissues (n=50) was examined by quantitative Real-time polymerase chain reaction (qRT-PCR). We further analyzed the correlation between miRNA-621 expression and pathological indexes of NSCLC patients. By transfection of miRNA-621 mimics, its expression was upregulated. Regulatory effects of miRNA-621 on proliferation and apoptosis of H1299 and SPC-A1 cells were evaluated by cell counting kit-8 (CCK-8), 5-Ethynyl-2’- deoxyuridine (EdU) assay and flow cytometry, respectively. Finally, the potential mechanism of miRNA-621 in regulating target gene SIX4 was explored by Western blot and rescue experiments.
RESULTS: MiRNA-621 was lowly expressed in NSCLC tissues relative to paracancerous tissues. NSCLC patients with low-level miRNA-621 were expected to have a worse clinical grade and shorter overall survival compared with those with a high level. Transfection of miRNA-621 mimics in H1299 and SPC-A1 cells markedly suppressed proliferation, but induced apoptosis. SIX4 was found to be highly expressed in NSCLC and negatively regulated by miRNA-621. MiRNA-621 overexpression could downregulate protein levels of SIX4, CD31, Ki-67, c-Myc, MMP-2 and MMP-9 in H1299 and SPC-A1 cells. Overexpression of SIX4 partially reversed the role of miRNA-621 in the malignant progression of NSCLC.
CONCLUSIONS: MiRNA-621 is closely related to pathological grade and poor prognosis of NSCLC. Besides, miRNA-621 can inhibit the malignant progression of NSCLC by regulating SIX4 expression.

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