PMID- 31169310 OWN - NLM STAT- MEDLINE DCOM- 20200611 LR - 20200611 IS - 1097-4652 (Electronic) IS - 0021-9541 (Linking) VI - 234 IP - 12 DP - 2019 Dec TI - Gene regulation and prognostic indicators of lung squamous cell carcinoma: TCGA-derived miRNA/mRNA sequencing and DNA methylation data. PG - 22896-22910 LID - 10.1002/jcp.28852 [doi] AB - Lung squamous cell carcinoma (LSCC) is a common cancer worldwide, and this study aimed to 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, TBL1XR1 as 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 ZEB2 and 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. CI - (c) 2019 Wiley Periodicals, Inc. FAU - Shen, Yuzhou AU - Shen Y AD - Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Pan, Xufeng AU - Pan X AD - Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Yang, Jun AU - Yang J AUID- ORCID: 0000-0003-2488-5408 AD - Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China. LA - eng PT - Journal Article DEP - 20190606 PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (Biomarkers, Tumor) RN - 0 (MicroRNAs) RN - 0 (Neoplasm Proteins) RN - 0 (RNA, Messenger) SB - IM MH - Biomarkers, Tumor/genetics MH - Carcinoma, Non-Small-Cell Lung/*genetics/pathology MH - Carcinoma, Squamous Cell/*genetics/pathology MH - Cell Line, Tumor MH - DNA Methylation/*genetics MH - Disease-Free Survival MH - Female MH - Gene Expression Regulation, Neoplastic/genetics MH - Gene Regulatory Networks/genetics MH - High-Throughput Nucleotide Sequencing MH - Humans MH - Male MH - MicroRNAs/*genetics MH - Neoplasm Proteins/genetics MH - Prognosis MH - RNA, Messenger/genetics OTO - NOTNLM OT - DNA methylation OT - lung squamous cell carcinoma OT - microRNA OT - the Cancer Genome Atlas OT - transcription factor EDAT- 2019/06/07 06:00 MHDA- 2020/06/12 06:00 CRDT- 2019/06/07 06:00 PHST- 2018/12/07 00:00 [received] PHST- 2019/03/15 00:00 [revised] PHST- 2019/05/01 00:00 [accepted] PHST- 2019/06/07 06:00 [pubmed] PHST- 2020/06/12 06:00 [medline] PHST- 2019/06/07 06:00 [entrez] AID - 10.1002/jcp.28852 [doi] PST - ppublish SO - J Cell Physiol. 2019 Dec;234(12):22896-22910. doi: 10.1002/jcp.28852. Epub 2019 Jun 6.