Background: Non-small cell lung cancer (NSCLC) is the main type of lung cancer, remaining a leading cause of cancer-related mortality around the world. Circular RNA SMARCA5 (circSMARCA5) is a novel circular RNA associated with the pathogenesis of several cancers. However, the role of circSMARCA5 in NSCLC remains unknown. In the present study, we aimed to evaluate the functions of circSMARCA5 in NSCLC and the underlying mechanism.
Methods: The expression pattern of circSMARCA5 was determined using qRT-PCR in NSCLC samples and cell lines. The correlation between miR-19b-3p and circSMARCA5 in NSCLC tissues was detected by qRT-PCR. Cell proliferation was examined utilizing CCK-8 assay. Cell migration and invasion was evaluated using Transwell assay. We used the bioinformatics software TargetScan and miRanda to predict circRNA-miRNA and miRNAi-mRNA interactions. Further, the regulatory role of circSMARCA5 in the malignant development of NSCLC in vivo was examined.
Results: The results showed that circSMARCA5 was down-regulated in NSCLC tissues as compared to the adjacent normal tissues. Overexpression of circSMARCA5 in NSCLC cell lines significantly inhibited the proliferation, migration, and invasion. Furthermore, circSMARCA5 exerted its tumor-suppressive activity through acting as a sponge for microRNA (miR)-19b-3p. Suppression of miR-19b-3p exhibited inhibitory effects on proliferation, migration, and invasion of NSCLC cell lines, which could be attributed to the regulation of homeobox A9 expression. Finally, overexpression of circSMARCA5 inhibited tumor growth in vivo.
Conclusion: Collectively, circSMARCA5 executed its inhibitory effects on NSCLC cell lines through miR-19b-3p/HOXA9 axis. The results indicated that circSMARCA5 might be a therapeutic target for the treatment of NSCLC.
Keywords: non-small cell lung cancer, NSCLC, circSMARCA5, miR-19b-3p, HOXA9, tumor suppressor