Identification Of Mir-133a-3p-Expression Signature And Probable Mechanism In Lung Squamous Cell Carcinoma: Insights From Integrated Analysis

Lung squamous cell carcinoma (LUSC) is the second largest subtype of lung cancer and have been suggested decreased in cancers, but the mechanism is still elusive. The objective of this study was to investigate the role of miR-133a-3p in LUSC and reveal the potential mechanism related to miR-133a-3p. In Gene Expression Omnibus (GEO) database, miRNA microarrays involved in LUSC were collected to conduct a meta-analysis. The results were validated in clinical samples by qRT-PCR. The miRNA sequencing data in LUSC were collected from The Cancer Genome Atlas (TCGA), and the different expression of pri-miR-133a between LUSC and non-cancerous tissues were analyzed. In LUSC cell microarrays, deregulated genes associated with miR-133a-3p were collected, combined with the predicted target genes by online tools, we then searched for potential target genes of miR-133a-3p. The target genes were enriched by Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Meta-analysis showed that miR-133a-3p was down-regulated in LUSC [ SMD (95% CI)=-1.18 (-1.90, -0.45)]. TCGA data demonstrated that miR-133a-1 (P<0.001, the area under the ROC curve (AUC)=0.961) and miR-133a-2 (P<0.001, AUC=0.794) were down-regulated in LUSC. The results were consistent with clinical samples in house (P<0.001, AUC=0.801). Five-hundred-twenty genes were identified as potential target genes of miR-133a-3p. They were mainly enriched in GO terms referring to nucleotide regulation. Endocytosis was the most significantly enriched KEGG pathway. miR-133a-3p were downregulated in LUSC, act as a suppressive miRNA in LUSC. Nucleotide regulated and endocytosis may be the mechanisms by which miR-133a-3p acts on LUSC.