ELK1‑mediated upregulation of lncRNA LBX2‑AS1 facilitates cell proliferation and invasion via regulating miR‑491‑5p/S100A11 axis in colorectal cancer.

Abstract

The aim of the present study was to investigate the role and regulatory mechanism of LBX2 antisense RNA 1 (LBX2-AS1) in colorectal cancer. Firstly, LBX2-AS1 expression was detected using reverse transcription-quantitative PCR in colorectal cancer tissues and cells, and its prognostic and diagnostic efficacy was assessed in a colorectal cancer cohort (n=145). Subcellular fractionation assay of LBX2-AS1 was performed. Secondly, the effects of LBX2-AS1 and microRNA (miR)-491-5p on colorectal cancer cell proliferation, apoptosis, migration and invasion were investigated by a series of functional assays. Thirdly, RNA immunoprecipitation, dual-luciferase reporter and gain and loss of function assays were carried out to analyze the interactions between ETS transcription factor ELK1 (ELK1) and LBX2-AS1, as well as LBX2-AS1, miR-491-5p and S100A11. The results showed that LBX2-AS1 was upregulated both in colorectal cancer tissues and cells, which was distributed in the cytoplasm and nucleus of colorectal cancer cells. Clinically, high LBX2-AS1 expression could be an independent prognostic factor for colorectal cancer. Furthermore, relative operating characteristic curve analysis showed that LBX2-AS1 was a sensitive diagnostic marker for colorectal cancer. Highly expressed ELK1, as a transcription factor, could bind to the two conserved sites in the promoter region of LBX2-AS1, thereby activating the transcription of LBX2-AS1. Silencing LBX2-AS1 markedly inhibited proliferative, migratory and invasive abilities of colorectal cancer cells. miR-491-5p expression was downregulated, while S100A11 expression was upregulated in colorectal cancer tissues and cells. Dual-luciferase reporter assays confirmed that LBX2-AS1 could block S100A11 degradation via competitively binding to miR-491-5p. Furthermore, LBX2-AS1 overexpression could notably reverse the inhibitory effect of miR-491-5p on proliferation and invasion of colorectal cancer cells. Taken together, LBX2-AS1 induced by transcription factor ELK1 may facilitate colorectal cancer cell proliferation and invasion via regulation of the miR-491-5p/S100A11 axis. Thus, LBX2-AS1 could be an underlying prognostic and diagnostic marker for colorectal cancer.