Comprehensive Analysis of CDK1-Associated ceRNA Network Revealing the Key Pathways LINC00460/LINC00525-Hsa-Mir-338-FAM111/ZWINT as Prognostic Biomarkers in Lung Adenocarcinoma Combined with Experiments

Wen Li; Shan-Shan Feng; Hao Wu; Jing Deng; Wang-Yan Zhou; Ming-Xi Jia; Yi Shi; Liang Ma; Xiao-Xi Zeng; Zavuga Zuberi; Da Fu; Xiang Liu; Zhu Chen

doi:10.3390/cells11071220

Comprehensive Analysis of CDK1-Associated ceRNA Network Revealing the Key Pathways LINC00460/LINC00525-Hsa-Mir-338-FAM111/ZWINT as Prognostic Biomarkers in Lung Adenocarcinoma Combined with Experiments

Cells. 2022 Apr 4;11(7):1220. doi: 10.3390/cells11071220.

Authors

Wen Li^{1

2}, Shan-Shan Feng¹, Hao Wu², Jing Deng¹, Wang-Yan Zhou³, Ming-Xi Jia², Yi Shi², Liang Ma¹, Xiao-Xi Zeng¹, Zavuga Zuberi⁴, Da Fu⁵, Xiang Liu⁶, Zhu Chen¹

Affiliations

¹ College of Life Sciences and Chemistry, Hunan University of Technology, Zhuzhou 412007, China.
² National Engineering Research Center of Rice and Byproduct Deep Processing, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, China.
³ Department of Medical Record, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang 421001, China.
⁴ Department of Science and Laboratory Technology, Dar es Salaam Institute of Technology, Dar es Salaam P.O. Box 2958, Tanzania.
⁵ Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
⁶ Department of Thoracic Surgery, Hengyang Medical School, The Second Affiliated Hospital, University of South China, Hengyang 421001, China.

Abstract

Lung adenocarcinoma (LUAD) is the leading cause of cancer deaths worldwide, and effective biomarkers are still lacking for early detection and prognosis prediction. Here, based on gene expression profiles of LUAD patients from The Cancer Genome Atlas (TCGA), 806 long non-coding RNAs (lncRNAs), 122 microRNAs (miRNAs) and 1269 mRNAs associated with CDK1 were identified. The regulatory axis of LINC00460/LINC00525-hsa-mir-338-FAM111B/ZWINT was determined according to the correlation between gene expression and patient prognosis. The abnormal up-regulation of FAM111B/ZWINT in LUAD was related to hypomethylation. Furthermore, immune infiltration analysis suggested FAM111B/ZWINT could affect the development and prognosis of cancer by regulating the LUAD immune microenvironment. EMT feature analysis suggested that FAM111B/ZWINT promoted tumor spread through the EMT process. Functional analysis showed FAM111B/ZWINT was involved in cell cycle events such as DNA replication and chromosome separation. We analyzed the HERB and GSCALite databases to identify potential target medicines that may play a role in the treatment of LUAD. Finally, the expression of LINC00460/LINC00525-hsa-mir-338-FAM111B/ZWINT axis was verified in LUAD cells by RT-qPCR, and these results were consistent with bioinformatics analysis. Overall, we constructed a CDK1-related ceRNA network and revealed the LINC00460/LINC00525-hsa-mir-338-FAM111/ZWINT pathways as potential diagnostic biomarkers or therapeutic targets of LUAD.

Keywords: CDK1 gene; FAM111B/ZWINT gene; LINC00525/LINC00460; Lung adenocarcinoma; ceRNA network; prognosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma* / genetics
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
CDC2 Protein Kinase / genetics
CDC2 Protein Kinase / metabolism
Cell Cycle Proteins
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Humans
Intracellular Signaling Peptides and Proteins / metabolism
Lung / pathology
Lung Neoplasms* / pathology
MicroRNAs* / genetics
MicroRNAs* / metabolism
Nuclear Proteins / metabolism
Prognosis
Tumor Microenvironment

Substances

Biomarkers, Tumor
Cell Cycle Proteins
FAM111B protein, human
Intracellular Signaling Peptides and Proteins
MIRN338 microRNA, human
MicroRNAs
Nuclear Proteins
ZWINT protein, human
CDC2 Protein Kinase
CDK1 protein, human