Biologie Cellulaire et Moléculaire

Abstrait

Detecting the Regulatory Mechanism of circ-CCND1 in Lung Adenocarcinoma

Pei Xu, Yixin Ding, Pengkai Gao, Lei Wang, Fengqing Hu, Xiao Xie, Lianyong Jiang, Rui Bi, Qingtao Liu, Haibo Xiao, Qi Yang, Fangbao Ding

Numerous circular RNAs (circRNAs) have been investigated in human malignancies, including lung adenocarcinoma. Previous investigations reported that circ-CCND1 (CCND1, deubiquitinylation of the G1 cyclin D1) functions in cancer progression, but its role as well as its regulatory mechanism remain unclear. The present study therefore aimed to identify the role of circ-CCND1 in lung adenocarcinoma progression. The circ-CCND1 expression and characteristics were separately analyzed using qRT-PCR. We used the CCK-8 assay, colony formation assay, western blotting, Transwell assay, and the luciferase reporter assay to characterize tumor growth and metastasis in vivo. The results demonstrated that circ-CCND1 expression increased in lung adenocarcinoma cell lines, and downregulated circ- CCND1-suppressed cell proliferation and migration. Bioinformatics analyses suggested that miR-503-5p and Sirtuin 5 (SIRT5) were circ-CCND1 downstream targets. The miR-503-5p downregulation or SIRT5 overexpression reversed migration and proliferation after knockdown of circ-CCND1. In vivo tests confirmed that downregulation of circ-CCND1 suppressed tumor formation and metastasis in nude mouse xenografts. In addition, western blotting showed that knockdown of circ-CCND1 suppressed the SIRT5-mediated, autophagy related proteins, Beclin-1 and light chain 3 (LC3) expressions. Taken together, this study showed that circ-CCND1 downregulation suppressed proliferation and migration through miR-503-5p/SIRT5-mediated autophagy regulation by sponging.