Circ_100565 promotes proliferation, migration and invasion in non-small cell lung cancer through upregulating HMGA2 via sponging miR-506-3p

Abstract

Background: Circular RNAs (circRNAs) play a vital role in the development of various cancers. Circ_100565 was found to be a highly expressed circRNA in non-small cell lung cancer (NSCLC) tissues screened by microarray profiles of circRNAs. However, the role of circ_100565 in NSCLC still remains unknown. Methods: Microarray analysis was used to screen for differentially expressed circRNAs in NSCLC tissues. The expression levels of circ_100565, microRNA-506-3p (miR-506-3p) and high mobility group AT-hook 2 (HMGA2) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was detected by cell counting kit-8 (CCK-8) and colony formation assays. Transwell assay was used to determine the migration and invasion of cells. Besides, Western blot (WB) analysis was performed to assess the levels of proliferation and metastasis-related proteins and HMGA2 protein. Moreover, animal experiments were used to confirm the effect of circ_100565 on NSCLC tumor growth in vivo. In addition, the interaction between miR-506-3p and circ_100565 or HMGA2 was confirmed by dual-luciferase reporter, RNA immunoprecipitation (RIP) assay or biotin-labeled pull-down assay. Results: Circ_100565 was upregulated in NSCLC, and its high expression was positively associated with the poor overall survival of NSCLC patients. Silencing of circ_100565 suppressed the proliferation, migration and invasion of NSCLC cells in vitro and reduced the tumor growth of NSCLC in vivo. Circ_100565 could sponge miR-506-3p, and miR-506-3p could target HMGA2. Moreover, miR-506-3p inhibitor or HMGA2 overexpression could reverse the inhibition effect of circ_100565 knockdown on NSCLC progression. Conclusion: Circ_100565 increased HMGA2 expression to promote proliferation, migration and invasion in NSCLC via absorbing miR-506-3p. Our findings provided a new biomarker for NSCLC therapy.