CircRNA BIRC6 promotes non-small cell lung cancer cell progression by sponging microRNA-145

• DOI: 10.1007/s13402-020-00503-x
• Publication Date: 2020-04-15T11:03:08Z
• Authors: Han Yang; Mengjing Zhao; Lihao Zhao; Ping Li; Yuxia Duan; Gang Li
• Keywords: Male; 0301 basic medicine; 0303 health sciences; Lung Neoplasms; Mice, SCID; RNA, Circular; Middle Aged; Xenograft Model Antitumor Assays; Up-Regulation; 3. Good health; Gene Expression Regulation, Neoplastic; MicroRNAs; 03 medical and health sciences; A549 Cells; Carcinoma, Non-Small-Cell Lung; Disease Progression; Animals; Humans; Gene Silencing; Cell Proliferation

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality world-wide. Recently, a number of circular RNAs (circRNAs) has been found to be differentially expressed in human NSCLCs, correlating with clinico-pathological features. As yet, the expression and potential role of circRNA BIRC6 (circBIRC6) in NSCLC have not been studied.Expression of circBIRC6 and its target microRNA-145 (miR-145) in human NSCLC cells and tissues was assessed using qRT-PCR. In vitro genetic strategies were used to exogenously alter circBIRC6 and miR-145 expression. Their impact on in vitro and in vivo NSCLC cell behavior was studied.We found that circBIRC6 was upregulated in primary human NSCLC tissues and NSCLC cells, whereas its potential target, miR-145, was downregulated. In A549 NSCLC cells and primary human NSCLC cells, shRNA-induced silencing of circBIRC6 potently inhibited their growth, proliferation, migration and invasion. Conversely, we found that exogenous overexpression of circBIRC6 promoted these characteristics. Using RNA immunoprecipitation (RIP) in A549 cells, we found that Argonaute 2 (Ago2) immunoprecipitated together with both circBIRC6 and miR-145. Additional studies revealed that the miR-145 level increased after circBIRC6 silencing in A549 cells, but decreased after circBIRC6 overexpression. Of note, we found that the circBIRC6 silencing-induced anti-A549 activity could be attenuated by a miR-145 inhibitor. Lastly, we found that circBIRC6 silencing inhibited the growth of NSCLC xenografts in severe combined immunodeficient mice.From our data we conclude that circBIRC6 overexpression promotes NSCLC cell progression, possibly by sponging miR-145.