circPDSS1 Stimulates the Development of Colorectal Cancer via Activating the Wnt/β-Catenin Signaling

Qun Fang; Aijie Yang; Anshan Dong; Ligang Zhao

doi:10.2147/OTT.S249853

circPDSS1 Stimulates the Development of Colorectal Cancer via Activating the Wnt/β-Catenin Signaling

Onco Targets Ther. 2020 Jun 30:13:6329-6337. doi: 10.2147/OTT.S249853. eCollection 2020.

Authors

Qun Fang^#¹, Aijie Yang^#², Anshan Dong³, Ligang Zhao⁴

Affiliations

¹ Department of Emergency, Yidu Central Hospital of Weifang, Weifang, People's Republic of China.
² Department of Radiotherapy, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, People's Republic of China.
³ Department of Gastroenterology, Weifang Second People's Hospital, Weifang, People's Republic of China.
⁴ Department of General Surgery, PLA Rocket Force Characteristic Medical Center, Beijing, People's Republic of China.

^# Contributed equally.

Abstract

Objective: This study aims to illustrate the role of circPDSS1 and the Wnt/β-catenin signaling in the development of colorectal cancer (CRC).

Patients and methods: Cancerous mucosa and normal paracancerous mucosa tissues more than 5 cm away from the tumor were surgically collected from 56 CRC patients. circPDSS1 levels in collected tissues and CRC cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The influence of circPDSS1 on clinical features of CRC patients was analyzed. After knockdown of circPDSS1 in HCT-8 and HCT-116 cells, phenotype changes were examined by Transwell, tube formation and wound healing assay. Western blot and rescue experiments were finally performed to uncover the role of circPDSS1 and the Wnt/β-catenin signaling in the development of CRC.

Results: circPDSS1 was upregulated in CRC mucosa tissues than controls. High level of circPDSS1 predicted high rates of lymphatic metastasis and distant metastasis, and poor prognosis in CRC patients. Knockdown of circPDSS1 attenuated migratory ability and angiogenesis in CRC cells. Protein levels of key genes in the Wnt/β-catenin signaling, including β-catenin, GSK-3β, c-Myc, MMP-9 and cyclin D1 were downregulated in CRC cells transfected with sh-circPDSS1. Overexpression of β-catenin reversed the role of circPDSS1 in attenuating migratory ability and angiogenesis in CRC cells.

Conclusion: Upregulated circPDSS1 in CRC is closely linked to lymphatic metastasis, distant metastasis and overall survival. It stimulates the migratory ability and angiogenesis in CRC cells via activating the Wnt/β-catenin signaling.

Keywords: CRC; Wnt/β-catenin; circPDSS1; metastasis.

Publication types

Retracted Publication