MicroRNA-20a-5p suppresses tumor angiogenesis of non-small cell lung cancer through RRM2-mediated PI3K/Akt signaling pat
- PDF / 3,268,789 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 58 Downloads / 158 Views
MicroRNA‑20a‑5p suppresses tumor angiogenesis of non‑small cell lung cancer through RRM2‑mediated PI3K/Akt signaling pathway Junlei Han1 · Jianping Hu1 · Fang Sun1 · Hongzhi Bian1 · Bingxiang Tang1 · Xiang Fang1 Received: 8 July 2020 / Accepted: 9 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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-ethynyl29-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. Keywords MicroRNA-20a · Ribonucleotide reductase regulatory subunit M2 · NSCLC · Angiogenesis Abbreviations NSCLC Non-small cell lung cancer miR-20a MiR-20a-5p RRM2 Ribonucleotide reductase regulatory subunit M2 LC Lung cancer 3′-UTRs 3′ Untranslated regions GEO Gene expression omnibus DEGs Differentially expressed genes BEAS-2B Human normal bronchial epithelial cell HUVEC Human umbilical vein endothelial cells DLR Dual-luciferase reporter assay FBS Fetal bovine serum RT Room temperature * Jianping Hu [email protected] 1
Respiratory and Critical Illness Ward 1, Henan Chest Hospital, No. 1, Weiwu Road, Zhengzhou 450000, Henan, China
Introduction Lung cancer (LC) exhibits rapid growth in morbidity and mortality both in male and female patients around the world [1]. Based on histology and etiology, LC can be classified into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). In China, NSCLC comprises appropriately 85% of newly diagnosed LC cases [2]. Although the th
Data Loading...
