Clinical value of microRNA-198-5p downregulation in lung adenocarcinoma and its potential pathways

Shi-Shuo Wang; Ye-Ying Fang; Jia-Cheng Huang; Yue-Ya Liang; Yi-Nan Guo; Lin-Jiang Pan; Gang Chen

doi:10.3892/ol.2019.10610

Clinical value of microRNA-198-5p downregulation in lung adenocarcinoma and its potential pathways

Oncol Lett. 2019 Sep;18(3):2939-2954. doi: 10.3892/ol.2019.10610. Epub 2019 Jul 12.

Authors

Shi-Shuo Wang¹, Ye-Ying Fang², Jia-Cheng Huang¹, Yue-Ya Liang¹, Yi-Nan Guo¹, Lin-Jiang Pan², Gang Chen¹

Affiliations

¹ Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
² Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Radiation Oncology Clinical Medical Research Center of Guangxi, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.

Abstract

Lung adenocarcinoma (LUAD), the main subtype of non-small cell lung cancer, is known to be regulated by various microRNAs (miRs/miRNAs); however, the role of miR-198-5p in LUAD has not been clarified. In the present study, the clinical value of miR-198-5p in LUAD and its potential molecular mechanism was evaluated. miR-198-5p expression was examined by reverse transcription-quantitative PCR (RT-qPCR) in 101 paired LUAD and adjacent normal lung tissues. Subsequently, the miR-198-5p expression level was determined from microarray data from the Gene Expression Omnibus, ArrayExpress and by meta-analyses. Furthermore, the target mRNAs of miR-198-5p from 12 miRNA-mRNA predictive tools were intersected with The Cancer Genome Atlas (TCGA)-based differentially expressed genes. In addition, Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to determine the possible mechanism of miR-198-5p in LUAD. The Search Tool for the Retrieval of Interacting Genes/Proteins database was employed to construct a protein-protein interaction network among the potential target genes of miR-198-5p. The results showed that miR-198-5p expression was lower in LUAD tissues than in adjacent non-cancerous lung tissues (4.469±2.495 vs. 5.301±2.502; P=0.015). Meta-analyses, including the data from the present study and online microarray data, also verified the downregulation of miR-198-5p in 584 cases of LUAD. The expression of miR-198-5p was associated with the age, blood vessel invasion, Tumor-Node-Metastasis stage, and lymph node metastasis of patients with LUAD and served as an independent prognostic factor for survival. The hub genes of miR-198-5p were upregulated in LUAD, according to TCGA and The Human Protein Atlas. For the KEGG pathway analysis, the most enriched KEGG pathway was the p53 signaling pathway (P=1.42×10^-6). These findings indicated that the downregulation of miR-198-5p may play a pivotal role in the development of LUAD by targeting various signaling pathways.

Keywords: bioinformatics; expression; lung adenocarcinoma; microRNA-198-5p; microarray; reverse transcription-quantitative PCR; target genes.