Downregulated Circular RNA hsa_circ_0000291 Suppresses Migration And Proliferation Of Gastric Cancer Via Targeting The miR-183/ITGB1 Axis

Chuanwu Cao,* Shilong Han,* Yifeng Yuan, Yongfa Wu, Weishuai Lian, Xiaojun Zhang, Long Pan, Maoquan Li Department of Interventional and Vascular Surgery, Tenth People’s Hospital of Tongji University, Shanghai 200072, People’s Republic of China*These authors contributed equally to this workCorrespondence: Maoquan LiDepartment of Interventional and Vascular Surgery, Tenth People’s Hospital of Tongji University, 301 Middle Yan Chang Road, Shanghai 200072, People’s Republic of ChinaTel +86-021-66313506Email cjr.limaoquan@vip.163.comBackground: Circular RNAs are implicated in a variety of cancers. This investigation found that hsa_circ_0000291 expression was upregulated in gastric cancer (GC) cell lines, yet its role in GC has not yet been reported.Objective: To explore the effects of hsa_circ_0000291 on GC cell proliferation and invasion.Materials and methods: In the current research, we used the gastric cancer cell lines MGC803 and MKN-28 to study hsa_circ_0000291 function. The relationship between hsa_circ_0000291, miR-183 and ITGB1 was analyzed by firefly luciferase analysis and Western blots, and qRT-PCR approaches were used for protein and gene expression analysis, respectively. Tumor growth and metastasis were determined in nude mice xenografts using MKN-28 cells, with or without hsa_circ_000r0291 downregulation.Results: Our data showed that hsa_circ_0000291 was upregulated in GC cell lines, whereas hsa_circ_0000291 silencing suppressed cell metastasis and proliferation in in vivo and in vitro studies. Our results showed that the downregulation of hsa_circ_0000291 suppressed integrin beta 1 (ITGB1) expression via miR-183 “sponging,” which was validated by rescue experiments using the luciferase reporter assay. Our observations suggested that hsa_circ_0000291 silencing suppressed the aggressive, metastatic GC phenotype.Conclusion: Taken together, hsa_circ_0000291 knockdown inhibited GC cell metastasis and growth by regulating the miR-183/ITGB1 axis. Importantly, this approach could provide a therapy target and potential biomarker for the diagnosis and treatment of GC.Keywords: hsa_circ_0000291, miR-183, integrin beta 1, proliferation and migration, gastric cancer