Integrated Analysis of lncRNAs and mRNAs Identifies a Potential Driver lncRNA FENDRR in Lung Cancer in Xuanwei, China

Abstract

This study was to screen out potential driver long non-coding RNAs (lncRNAs) in lung cancer in Xuanwei (LCXW) differently expressed mRNAs and lncRNAs were detected by gene expression microarrays in 23 paired lung adenocarcinoma and adjacent tissues. Combined bioinformatics analysis was performed to identify potential driver lncRNAs and their potential regulatory relationships. Transcriptome and clinical data in TCGA-LUAD were used as comparison and validation dataset. The comparison of LCXW and TCGA-LUAD revealed significant differences in expression of some genes, signaling pathways affected by differentially expressed genes, and the 5-year survival rate of patients. We identified 14 consistently deregulated mRNAs and 5 lncRNAs as candidate genes, which affected multiple cancer-related pathways and influenced patients’ overall survival. By combined bioinformatics analysis, we further identified a potential driver lncRNA fetal-lethal non-coding developmental regulatory RNA (FENDRR) and proposed its possible regulation mechanism. The low expression of FENDRR was positively correlated with Krüppel-like factor4 (KLF4), KLF4 down-regulation may loss the activation function of cyclin-dependent kinase inhibitor 1A (CDKN1A) and cyclin-dependent kinase inhibitor 1C (CDKN1C) and the inhibition function of CyclinB1 (CCNB1), eventually cause excessive cell cycle activation and lead to lung cancer. This study revealed a potential FENDRR-KLF4-cell cycle regulation axis. These results lay an important foundation for further research on the pathogenesis of LCXW and identification of potential novel biomarkers or therapeutic targets.

Declaration of Interest

No potential conflict of interest was reported by the author(s).

Availability of Data and Materials

TCGA-LUAD transcriptome and clinical data were downloaded from the Genomic Data Commons (GDC) Data Portal (https://portal.gdc.cancer.gov/)

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (Grant Nos. 81660388, 81460325), Applied Basic Research Project of Science and Technology Department of Yunnan Province-Kunming Medical University Union Fund (2017FE467(-131)), Training Program for 100 Young and Middle-aged Academic and Technical Leaders of Kunming Medical University (60117190460), Project of In-house Research Institutions in Yunnan Medical and Health Units (2016NS031). We gratefully acknowledge the participation of all the participants and the support of above projects.