Lung squamous cell carcinoma (LUSC) is the main pathological type of pulmonary malignant tumors; at present, less than 10% of patients with advanced metastatic LUSC live for more than 5 years. We previously reported that low expression of miRNA‐126‐3p is associated with the occurrence and progression of lung adenocarcinoma (LUAD). Here, we examined expression of miRNA‐126‐3p in 23 samples from patients with LUSCs and 23 normal control specimens by quantitative real‐time PCR (RT‐qPCR). Associations between miRNA‐126‐3p expression and clinical features were studied from materials derived from Gene Expression Omnibus (GEO) chips and The Cancer Genome Atlas (TCGA) database. Twelve online platforms were used to identify candidate target genes of miRNA‐126‐3p. Further analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and protein–protein interaction (PPI) network were performed on the target genes. GEO microarray analysis, TCGA data mining, RT‐qPCR, and integration analysis consistently reported low expression of miRNA‐126‐3p in LUSC. A total of 42 genes were identified as potential target genes of miRNA‐126‐3p from online platforms, GEO microarrays, and the TCGA database. GO and KEGG analyses demonstrated that the target genes are involved in several biological processes that promote the progression of LUSC. SOX2, E2F2, and E2F3 were selected as hub genes from the PPI network for further analysis. In summary, our results suggest that the low expression of miRNA‐126‐3p may play a role in promoting the development of LUSC and miRNA‐126‐3p may be a biomarker for LUSC early diagnosis and prognosis.
