Implication of Downregulation and Prospective Pathway Signaling of microRNA-375 in Lung Squamous Cell Carcinoma

Publication date: Available online 22 January 2017
Source:Pathology - Research and Practice
Author(s): Wen-jie Chen, Ting-qing Gan, Hui Qin, Su-ning Huang, Li-hua Yang, Ye-ying Fang, Zu-yun Li, Lin-jiang Pan, Gang Chen
BackgroundLung cancer is one of the most typical cancers in the world. Altered expression profiles of microRNA-375(miR-375) are linked to many diseases including lung cancer. However, the relationship between miR-375 and lung squamous cell carcinoma (LUSC) is controversial.MethodsWe first evaluated the 23 LUSCs and the paired normal lung tissues by qRT-PCR. Then we analyzed the LUSC samples with miR-375 expression based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Furthermore, bioinformatics analysis was performed to explore the biological role of miR-375 in LUSC.ResultsThe expression of miR-375 was remarkably reduced in LUSC tissues compared with that in paired lung tissues by qRT-PCR (P=0.003). Additionally, the TCGA dataset suggested that miR-375 was significantly downregulated in 478 LUSC tissues compared with 45 normal lung tissues (P<0.0001), as well as the result derived from GEO datasets (the pooled SMD=−1.01; 95%CIs-1.66 to −0.33, P=0.004). Furthermore, a total of 1348 miR-375-related differently expressed genes were identified by the analytical integration, which were involved in critical pathways of LUSC like neuron differentiation, plasma membrane part and sequence-specific DNA binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway examination also unveiled the involvement of target genes in morphine addiction and drug metabolism- other enzymes and neuroactive ligand-receptor interaction. Finally, the expression of WNT5A was inversely correlated with miR-375 expression according to TCGA dataset (r=−0.2342, P<0.0001).ConclusionsmiR-375 exerts a strong tumor-suppressive effect in LUSC and provided novel insight into the biological function in tumorigenesis and progression of LUSC.



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