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Research Paper|Volume 13, Issue 11|pp 14968—14988

Construction of a novel mRNA-miRNA-lncRNA network and identification of potential regulatory axis associated with prognosis in colorectal cancer liver metastases

Chen Lu1, Xiagang Luo1, Cheng Xing1, Yonghuan Mao1, Yuting Xu3, Wenjie Gao1, Wulin Wang4, Tian Zhan1, Guoguang Wang1, Zhengxia Liu2, Chunzhao Yu1
  • 1Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu, China
  • 2Department of Geriatrics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu, China
  • 3Department of Ophthalmology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China
  • 4Department of Gastrointestinal Surgery, Jingzhou Central Hospital, Jingzhou 434000, Hubei, China
* Equal contribution
Received: August 14, 2020Accepted: April 29, 2021Published: June 3, 2021
https://doi.org/10.18632/aging.203049

Copyright: © 2021 Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Liver metastasis is a leading cause of death in patients with colorectal cancer (CRC). Increasing evidence demonstrates that competing endogenous RNA (ceRNA) networks play important roles in malignant cancers. The purpose of this study was to identify molecular markers and build a ceRNA network as a significant predictor of colorectal liver metastases (CRLM). By integrated bioinformatics analysis, we found that apolipoprotein C1 (APOC1) was upregulated in CRLM and associated with prognosis in patients with CRC and thereby established an APOC1-dependent ceRNA network. By survival analysis, expression analysis, and correlation analysis of each element in the ceRNA network, we identified that ZEB1-AS1, miR-335-5p and APOC1 regulated each other. We further experimentally confirmed that ZEB1-AS1 promoted a CRC progression via regulating the expression of miR-335-5p that controlled the expression of APOC1. Our findings indicate that the ZEB1-AS1-miR-335-5p-APOC1 ceRNA regulatory network is significantly valuable for better prognosis of patients with CRC and as a new therapeutic target for the treatment of CRLM.