MicroRNA-20a-5p suppresses tumor angiogenesis of non-small cell lung cancer through RRM2-mediated PI3K/Akt signaling pathway

• Published in: Molecular and cellular biochemistry Vol. 476; no. 2; pp. 689 - 698
• Main Authors: Han, Junlei, Hu, Jianping, Sun, Fang, Bian, Hongzhi, Tang, Bingxiang, Fang, Xiang
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-02-2021; Springer; Springer Nature B.V
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Analysis; Angiogenesis; Assaying; Biochemistry; Bioinformatics; Biomedical and Life Sciences; Biotechnology; Cardiology; Cell adhesion & migration; Cell migration; Cell proliferation; Endothelial cells; Health aspects; In vivo methods and tests; Life Sciences; Lung cancer; Lung cancer, Non-small cell; Lung cancer, Small cell; Medical Biochemistry; Metastases; Metastasis; MicroRNA; MicroRNAs; miRNA; Non-small cell lung carcinoma; Oncology; Polymerase chain reaction; Reductases; Signal transduction; Signaling; Small cell lung carcinoma; Tumor suppressor genes; Tumors; Angiogenesis; Ribonucleotide reductase regulatory subunit M2; NSCLC; MicroRNA-20a
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-020-03936-y

The current therapeutic strategies for non-small cell lung cancer (NSCLC) are limited and unsatisfactory. MicroRNAs (miRNAs) participate in tumor angiogenesis in NSCLC. The aim of this study was to investigate the role of miR-20a-5p (miR-20a) in human NSCLC metastasis. In the current study, bioinformatics analysis and RT-PCR were performed to examine the expression level of miR-20a in tissues of NSCLC patients and NSCLC cell lines, respectively. Western blot was performed to test the protein levels. Cell proliferation, migration and angiogenesis capacity were tested by 5-ethynyl-29-deoxyuridine (EdU) assay, transwell assay and tube formation assay, respectively. Dual-luciferase reporter assay (DLR) was used to confirm the interaction between miR-20a and paired ribonucleotide reductase regulatory subunit M2 (RRM2). We found that the expression of RRM2 was upregulated, while the expression of miR-20a was downregulated in cancer tissues compared with adjacent tissues in NSCLC patients. We also detected the expression level of RRM2 and miR-20a in NSCLC cell lines, showing A549 cell line exhibited the lowest expression level of miR-20a and highest expression level of RRM2. Overexpressed miR-20a not only dramatically suppressed NSCLC cells proliferation, endothelial cells migration and tube formation in vitro, but also inhibited tumor growth and angiogenesis in vivo. It was demonstrated that miR-20a suppressed NSCLC growth by inhibiting RRM2-mediated PI3K/Akt signaling pathway. These findings indicate that the novel identified miR-20a could function as a tumor suppressor in NSCLC through modulating the RRM2-mediated PI3K/Akt axis, and it could be a valid molecular target for NSCLC treatment.