Clinical significance of high expression of miR-452-5p in lung squamous cell carcinoma

Xiao-Ning Gan; Ting-Qing Gan; Rong-Quan He; Jie Luo; Rui-Xue Tang; Han-Lin Wang; Hong Zhou; Hui Qing; Jie Ma; Xiao-Hua Hu; Gang Chen

doi:10.3892/ol.2018.8088

Clinical significance of high expression of miR-452-5p in lung squamous cell carcinoma

Oncol Lett. 2018 May;15(5):6418-6430. doi: 10.3892/ol.2018.8088. Epub 2018 Feb 20.

Authors

Xiao-Ning Gan¹, Ting-Qing Gan², Rong-Quan He², Jie Luo², Rui-Xue Tang¹, Han-Lin Wang¹, Hong Zhou¹, Hui Qing¹, Jie Ma², Xiao-Hua Hu², Gang Chen¹

Affiliations

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

Abstract

The role of microRNA (miRNA)-452-5p in lung squamous cell carcinoma (LUSC) remains unclear. Therefore, the present systematic study was performed to investigate the clinical significance and the rudimentary mechanism of the function of miR-452-5p in LUSC. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to confirm the expression level and clinical value of miR-452-5p in LUSC. Using online databases and bioinformatic software, gene ontology (GO), pathway and protein-protein interaction (PPI) analyses of miR-452-5p target genes were performed to examine the molecular mechanism of miR-452-5p. The association between the expression of miR-452-5p and that of its hub genes was verified using TCGA. Based on TCGA data on 387 clinical specimens, the expression of miR-452-5p in LUSC was significantly increased compared with adjacent lung tissues (7.1525±1.39063 vs. 6.0885±0.35298; P<0.001). The expression levels of miR-452-5p were significantly correlated with age (P=0.001) and tumor-node metastasis stage (P=0.028). Furthermore, the increased expression of miR-452-5p in LUSC compared with non-cancerous tissue [standard mean deviation (SMD), 0.372; 95% confidence interval (CI), 0.020-0.724; z=2.07; P=0.038] was validated by a meta-analysis of 720 clinical samples. The GO and pathway analyses revealed that miR-452-5p target genes were mainly enriched in the 'regulation of transcription', 'nucleoplasm', 'protein binding' and 'cell cycle' pathways. A total of 10 hub genes were identified by PPI analysis, and 5 hub genes (SMAD4, SMAD2, CDKN1B, YWHAE and YWHAB) were significantly enriched in the 'cell cycle' pathway. The expression of CDKN1B was negatively correlated with miR-452-5p (P=0.003). It was concluded that miR-452-5p may serve an essential role in the occurrence and progression of LUSC by targeting CDKN1B, which is involved in the cell cycle.

Keywords: Gene Expression Omnibus; The Cancer Genome Atlas; clinicopathological parameter; cyclin dependent kinase inhibitor 1B; lung squamous cell carcinoma; microRNA-452-5p.