CircTUBGCP3 Contributes to the Malignant Progression of Rectal Cancer.

Abstract

Circular RNA (circRNA) tubulin gamma complex associated protein 3 (circTUBGCP3) has been reported to play an oncogenic role in colorectal cancer and osteosarcoma. We further assessed the role and working mechanism of circTUBGCP3 in rectal cancer progression. Colony formation assay and transwell assays were performed to analyze cell colony formation ability and motility. Flow cytometry was utilized to assess cell cycle progression and cell apoptosis. The production of lactate and the consumption of glucose were evaluated by fluorescence-based glucose/lactate assay kit to analyze cell glycolysis. The intermolecular interaction was verified by dual-luciferase reporter assay. In vivo experiments were carried out to analyze the role of circTUBGCP3 in tumor growth using xenograft tumor model. CircTUBGCP3 was significantly up-regulated in rectal cancer tissues and cell lines. CircTUBGCP3 interference inhibited the colony formation ability, migration, invasion, cell cycle progression, and glycolysis and promoted the apoptosis in rectal cancer cells. CircTUBGCP3 negative regulated microRNA-375 (miR-375) expression through interacting with it and circTUBGCP3 silencing-mediated effects in rectal cancer cells were largely based on the up-regulation of miR-375. Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) was a target of miR-375, and ROCK1 was regulated by circTUBGCP3/miR-375 axis in rectal cancer cells. MiR-375 overexpression suppressed the malignant behaviors of rectal cancer cells partly through down-regulating ROCK1. CircTUBGCP3 interference restrained rectal cancer progression in vivo. CircTUBGCP3 acted as an oncogene to promote the malignant phenotypes of rectal cancer cells by modulating miR-375/ROCK1 axis.