circPTEN suppresses colorectal cancer progression through regulating PTEN/AKT pathway

Abstract

Recently, circular RNAs (circRNAs) have attracted growing attention due to their pivotal roles in the complicated cellular processes of diverse human malignancies, including colorectal cancer (CRC). Phosphatase and tensin homolog (PTEN) is known as a typical tumor-suppressing gene. Nevertheless, limited investigation on the function of circRNAs generated from PTEN has been undertaken. In this research, hsa_circ_0094343 (circPTEN) was found to display low expression in CRC tissues and cells. CircPTEN is characterized with high stability due to its circular structure. Upregulation of circPTEN suppressed CRC cell proliferation, migration, and invasion but facilitated apoptosis. Data from mechanism assays revealed that circPTEN could elevate PTEN expression through sequestering microRNA-4470 (miR-4470) in CRC cells. Further, circPTEN was validated to inhibit K63-linked ubiquitination of protein kinase B (AKT) and AKT phosphorylation at Thr-308 and Ser-473 by competitively binding with tumor necrosis factor (TNF)-receptor-associated factor 6 (TRAF6). Moreover, the results of rescue assays indicated that the suppressive effect of circPTEN on CRC progression could be totally reversed by overexpression of insulin like growth factor 1 (IGF-1) or partially reversed by knockdown of PTEN. To conclude, circPTEN suppresses CRC progression via regulation of PTEN/AKT pathway.

Keywords

• colorectal cancer
• circPTEN
• miR-4470
• AKT
• TRAF6