Gene regulation and prognostic indicators of lung squamous cell carcinoma: TCGA‐derived miRNA/mRNA sequencing and DNA methylation data

Abstract

Lung squamous cell carcinoma (LSCC) is a common cancer worldwide, and this study aimedto investigate the key regulatory networks and prognostic indicators of LSCC. MicroRNA (miRNA)/messenger RNA (mRNA) sequencing and DNA methylation data were obtained from the Cancer Genome Atlas. Differentially expressed miRNAs (DEmiRNAs) and genes (DEGs) were identified by the limma package. Then, the transcription factors (TFs) of DEmiRNAs/DEGs, as well as the targets of miRNAs, were predicted by the TFmiR online tool. Using the t test, aberrant methylation was detected in TF binding sites (TFBSs) in promoters. Finally, integrated network and survival analyses were conducted using SPSS software. We obtained 104 DEmiRNAs and 4,491 DEGs, and validated 2,113 DEGs (VDEGs). Then, 103 TFs, 295 TFs, and 14 DEmiRNAs were predicted to target 95 DEmiRNAs, 821 DEGs and 283 DEGs, respectively. After TF-DEmiRNA/DEG and TF-DEmiRNA-DEG networks were constructed (e.g., E2F1-CDC25A, miR29a-RAN, miR326-TBL1XR1), five feedforward loops between ZEB1 and miR-141/200a/200b/200c/429 were found. Furthermore, VDEGs CDC25A, RAN, TBL1XR1as well as miR-130b and miR-590 were negatively correlated with survival rates. E2F1-CDC25A, miR29a-RAN, miR326-TBL1XR1, and the feedforward loops between ZEB1/ZEB2 and miR-141/200a/200b/200c/429 might participate in LSCC development. Compared with BEAS-2B cells, the SK-MES-1 cells presented a higher expression level of miR-141, miR-200a, miR-200b, miR-200c but a lower expression level of ZEB1. Overexpressed miR-200c significantly attenuated the expression of ZEB1 and ZEB2and inhibited the proliferation and migration of SK-MES-1 cells (all p < 0.05). In addition, CDC25A, miR-200a, miR-200b, miR-200c, miR-130b, and miR-590 are potential prognostic indicators of LSCC.