CircRNA circ_0004370 promotes cell proliferation, migration, and invasion and inhibits cell apoptosis of esophageal cancer via miR-1301-3p/COL1A1 axis

Xiaobo Chen; Hongwen Sun; Yunping Zhao; Jing Zhang; Guosheng Xiong; Yue Cui; Changcheng Lei

doi:10.1515/med-2021-0001

CircRNA circ_0004370 promotes cell proliferation, migration, and invasion and inhibits cell apoptosis of esophageal cancer via miR-1301-3p/COL1A1 axis

Open Med (Wars). 2021 Jan 4;16(1):104-116. doi: 10.1515/med-2021-0001. eCollection 2021.

Authors

Xiaobo Chen¹, Hongwen Sun¹, Yunping Zhao¹, Jing Zhang¹, Guosheng Xiong¹, Yue Cui¹, Changcheng Lei¹

Affiliation

¹ Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, No 295 Xichang Road, Kunming 650032, Yunnan, China.

Abstract

Background: The aim of this study was to investigate the circ_0004370 expression in EC, its effects on cell proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT) process, and the underlying regulatory mechanisms in EC.

Methods: The protein levels of COL1A1 and EMT-related proteins were detected by western blot. The role of circ_0004370 on cell viability, proliferation, and apoptosis was analyzed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and flow cytometry, respectively. The transwell assay was used to examine cell migration and invasion. The binding sites between miR-1301-3p and circ_0004370 or COL1A1 were predicted by starbase software and confirmed by dual-luciferase reporter assay and RNA pull-down assay.

Results: We discovered that circ_0004370 was remarkably upregulated in EC tissues and cells. Knockdown of circ_0004370 inhibited cell proliferation, migration as well as invasion, and promoted apoptosis in vitro, while its effect was rescued by miR-1301-3p inhibition. And circ_0004370 mediated the EMT process in EC cells. Moreover, we explored its regulatory mechanism and found that circ_0004370 directly bound to miR-1301-3p and COL1A1 was verified as a target of miR-1301-3p. COL1A1 was highly expressed in EC cells and upregulation of COL1A1 reversed the effects of miR-1301-3p on cell proliferation, migration, invasion, and apoptosis. In addition, silencing of circ_0004370 reduced tumor volumes and weights in vivo. We showed that circ_0004370/miR-1301-3p/COL1A1 axis played the critical role in EC to regulate the cell activities.

Conclusion: Circ_0004370 promotes EC proliferation, migration and invasion, and EMT process and suppresses apoptosis by regulating the miR-1301-3p/COL1A1 axis, indicating that circ_0004370 may be used as a potential therapeutic target for EC.

Keywords: COL1A1; circ_0004370; esophageal cancer; miR-1301-3p.