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

Ma,Gang; Dai,Weijie; Zhang,Juan; Li,Qianjun; Gu,Biao; Song,Yaqi; Yang,Xiaozhong

doi:10.3892/ijmm.2021.4971

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

Authors:
- Gang Ma
- Weijie Dai
- Juan Zhang
- Qianjun Li
- Biao Gu
- Yaqi Song
- Xiaozhong Yang
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Affiliations: Division of Gastroenterology, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China, Department of Thoracic Surgery, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China, Department of Radiation Oncology, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
Published online on: May 26, 2021 https://doi.org/10.3892/ijmm.2021.4971
Article Number: 138
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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