Long noncoding RNA XIST knockdown suppresses the growth of colorectal cancer cells via regulating microRNA-338-3p/PAX5 axis

Colorectal Cancer

Eur J Cancer Prev. 2020 Aug 18. doi: 10.1097/CEJ.0000000000000596. Online ahead of print.


BACKGROUND: Colorectal cancer is one of the most common human cancers worldwide. Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have been reported as the regulators in cancers. The purpose of this study was to reveal the functional mechanisms of lncRNA x inactive specific transcript (XIST) and miR-338-3p in colorectal cancer cells.

METHODS: The transcription level and protein level of genes were assessed by quantitative real-time PCR (qRT-PCR) and western blot assay, respectively. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry analysis were used to determine cell proliferation ability and apoptosis rate, respectively. In addition, cell migratory ability and invasive ability were measured using transwell assay. Besides, the interaction between miR-338-3p and XIST or paired box 5 (PAX5) was predicted by starBase or TargetScan and then verified by the dual-luciferase reporter assay.

RESULTS: XIST and PAX5 expression were increased, and miR-338-3p expression was decreased in colorectal cancer tissues and cells. XIST knockdown significantly repressed cell proliferation, migration and invasion, and accelerated apoptosis in colorectal cancer cells. Interestingly, XIST directly downregulated miR-338-3p expression to increase PAX5 level. As expected, XIST knockdown inhibited colorectal cancer cell growth by modulating miR-338-3p expression. Furthermore, miR-338-3p suppressed cell growth via downregulation of PAX5 level in colorectal cancer cells.

CONCLUSION: Our results demonstrated that the downregulation of XIST inhibited cell proliferation, migration and invasion, and induced apoptosis through modulating miR-338-3p/PAX5 axis in colorectal cancer cells, providing potential target for the prevention and treatment of colorectal cancer.