FOXO1-Induced miR-502-3p Suppresses Colorectal Cancer Cell Growth through Targeting CDK6

Abstract

Colorectal cancer (CRC) is the most common tumor of the digestive system and the third most common tumor worldwide. To date, the prognosis of CRC patients remains poor. It is urgent to identify new therapeutic targets for CRC. As a tumor suppresser, microRNA (miRNA) miR-502-5p is downregulated in CRC tissues. Nevertheless, the role of miR-502-3p in CRC is largely unclear. Besides, the transcript factor forkhead box protein O1 (FOXO1) could suppress the CRC cell growth. However, the effect of FOXO1 on miR-502-3p in CRC remains unknown. By contrast, cyclin-dependent kinases 6 (CDK6) promotes the CRC cell growth. Yet the regulatory effect of miR-502-3p on CDK6 in CRC has not been reported. Thus, the primary aim of this study was to investigate whether FOXO1 enhanced miR-502-3p expression to suppress the CRC cell growth by targeting CDK6. Here, RNA level and protein level were detected by quantitative reverse transcription-PCR (qRT-PCR) and western blot (WB), respectively. Besides, the cell growth was detected by Cell Counting Kit 8 (CCK8) assay. Moreover, the regulatory effect of FOXO1 on miR-502-3p or miR-502-3p on CDK6 was determined using dual-luciferase reporter gene (DLR) assay. Results revealed that miR-502-3p and FOXO1 were downregulated in CRC cells. Besides, miR-502-3p suppressed the CRC cell growth. Moreover, FOXO1 could increase the miR-502-3p level through facilitating MIR502 transcription in CRC cells. In addition, miR-502-3p could suppress the CRC cell growth by targeting CDK6. These findings indicated that FOXO1 induced miR-502-3p expression to suppress the CRC cell growth through targeting CDK6, which might provide new therapeutic targets for CRC.

FOXO1：An Indicator for Prognosis of Lung Adenocarcinoma and Squamous Carcinoma from a Comprehensive Analysis of Bioinformatics

“…FOXO1, the rst transcription factor to be identi ed among the FOXO family, holds a pivotal position on chromosome 13 and gives rise to the FOXO1 protein [7,8]. Extensive research has been undertaken to elucidate the functional role of the FOXO1 protein in tumours, revealing its frequent inactivation in various human cancers and its potential as a tumour suppressor [9][10][11]. Of particular signi cance is the critical involvement of the FOXO1 protein in modulating several downstream proin ammatory factors, including the regulation of IL-10 release during the chronic in ammatory phase, thereby exerting an in uence on the immune system's response [12][13][14].…”