Propofol postpones colorectal cancer development through circ_0026344/miR-645/Akt/mTOR signal pathway

Open Med (Wars). 2021 Apr 7;16(1):570-580. doi: 10.1515/med-2021-0254. eCollection 2021.

Abstract

Colorectal cancer (CRC) is responsible for thousands of slow and painful annual deaths. Propofol, an anesthetic, is commonly used in CRC surgery. The role of circularRNA0026344 (circ_0026344) in propofol-treated CRC remains unclear, which was further explored in this study. Real-time polymerase chain reaction (qPCR) was used to detect the expression of circ_0026344 and microRNA645 (miR-645) in CRC cells and normal cells. Western blot was devoted to testing the protein expression of phospho-protein kinase B (p-AKT), AKT, phospho-mammalian target of rapamycin (p-mTOR), and mTOR in CRC cells. Moreover, cell counting kit-8 (CCK8), colony formation, flow cytometry, and transwell assays were employed to assess the proliferation, apoptosis, and metastasis in CRC cells. Circinteractome online tool was applied to predict the combination between circ_0026344 and miR-645, which was further verified by dual-luciferase reporter system. circ_0026344 was lowly expressed and miR-645 was abundantly expressed in CRC cells. The relative protein expression of p-AKT/AKT and p-mTOR/mTOR was strikingly elevated by si-circ#1, which could be reversed by anti-miR-645 in propofol-treated CRC cells. circ_0026344 overexpression inhibited the proliferation and metastasis and promoted apoptosis in CRC cells. Propofol treatment induced the restraint in proliferation and metastasis and stimulation in apoptosis, which were allayed by si-circ#1; meanwhile, this alleviation could further be abolished by anti-miR-645 in CRC cells. Furthermore, circ_0026344 sponged miR-645 to inhibited Akt/mTOR signal pathway in propofol-treated CRC cells. Propofol postponed CRC process by circ_0026344/miR-645/Akt/mTOR axis. This finding might provide a possibility to improve the therapy of CRC with propofol.

Keywords: Akt/mTOR; circ_0026344; colorectal cancer; miR-645; propofol.