Circular RNA hsa_circ_0014130 Inhibits Apoptosis in Non–Small Cell Lung Cancer by Sponging miR-136-5p and Upregulating BCL2

Abstract
Previous studies indicated that circular RNAs (circRNAs) played vital roles in the development of non-small-cell lung cancer (NSCLC). Although hsa_circ_0014130 might be a potential NSCLC biomarker, its function in NSCLC remains unknown. Thus, this study aimed to investigate the role of hsa_circ_0014130 in the progression of NSCLC. The levels of hsa_circ_0014130 in NSCLC tissues and adjacent normal tissues were determined by RT-qPCR. In addition, the expressions of Bcl-2, cleaved caspase 3 in A549 cells were detected with western blot. Meanwhile, the dual luciferase reporter system assay was used to determine the interaction of hsa_circ_0014130 and miR-136-5p, or Bcl-2 and miR-136-5p in NSCLC respectively. The level of hsa_circ_0014130 was significantly upregulated in NSCLC tissues. Downregulation of hsa_circ_0014130 markedly inhibited the proliferation and invasion of A549 cells via inducing apoptosis. In addition, downregulation of hsa_circ_0014130 inhibited the tumorigenesis of subcutaneous A549 xenograft in mice in vivo. Meanwhile, mechanistic analysis indicated that downregulation of hsa_circ_0014130 decreased the expression of miR-136-5p targeted gene Bcl-2 via acting as a competitive 'sponge' of miR-136-5p. In this study, we found that hsa_circ_0014130 was upregulated in NSCLC tissues. In addition, hsa_circ_0014130 functions as a tumor promoter in NSCLC to promote tumor growth through up-regulating Bcl-2 partially via 'sponging' miR-136-5p. Implications: In conclusion, hsa_circ_0014130 might function as a prognostic factor for patients with NSCLC and might be a therapeutic target for the treatment of NSCLC in future.