Comprehensive bioinformatics analysis identifies lncRNA HCG22 as a migration inhibitor in esophageal squamous cell carcinoma

• Published in: Journal of cellular biochemistry 2020-01, Vol.121 (1), p.468-481
• Main Authors: Li, Xizhe, Xiao, Xiaoxiong, Chang, Ruimin, Zhang, Chunfang
• Format: Article
• Language: English
• Subjects: ADAMTS1 Protein - genetics; ADAMTS1 Protein - metabolism; Apoptosis; Bioinformatics; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer; Cell adhesion & migration; Cell migration; Cell Movement; Cell Proliferation; Computational Biology - methods; Encyclopedias; Esophageal cancer; Esophageal Neoplasms - genetics; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - pathology; esophageal squamous cell carcinoma; Esophageal Squamous Cell Carcinoma - genetics; Esophageal Squamous Cell Carcinoma - metabolism; Esophageal Squamous Cell Carcinoma - pathology; Esophagus; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Genes; Genomes; HCG22; Humans; Inhibitors; lncRNA; Polymerase chain reaction; Prognosis; RNA, Long Noncoding - genetics; Serine Peptidase Inhibitors, Kazal Type - genetics; Serine Peptidase Inhibitors, Kazal Type - metabolism; Squamous cell carcinoma; Survival Rate; Tissues; Tumor Cells, Cultured; Tumors
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.29218

Esophageal cancer is one of the most lethal malignancies worldwide, and esophageal squamous cell carcinoma (ESCC) is the dominant histological type. However, the long noncoding RNA (lncRNA) alterations in ESCC have not been elucidated to date. In this study, reliable databases from Gene Expression Omnibus (GEO), which analyzed lncRNA expression in ESCC tumor tissues and adjacent normal tissues were searched, and common differentially expressed lncRNAs and genes were analyzed. Next, cis‐ trans analysis was performed to predict the underlying relationships between altered lncRNAs and mRNAs, and the lncRNA‐mRNA regulatory network was established. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of altered lncRNA‐related genes were performed. The promising lncRNA HCG22 was validated by quantitative polymerase chain reaction (qPCR), and clinicopathological data were collected to identify the relationship between lncRNA HCG22 expression level and clinical features. Finally, Transwell assays were performed to explore the biological functions of lncRNA HCG22 in ESCC cells. Two hundred forty‐one lncRNAs and 835 mRNAs were observed to be remarkably altered between ESCC tumor tissues and adjacent normal tissues. The lncRNA‐mRNA regulatory network showed the coexpression association between lncRNA HCG22 and SPINK7 and ADAMTS12. GO and KEGG analyses showed that HCG22 and ADAMTS12 had potential biological functions in the cell migration of ESCC. The downregulation of lncRNA HCG22 in ESCC tumor tissues was validated by qPCR, and the clinicopathological data showed a noticeable correlation between lncRNA HCG22 expression level and the ESCC differentiational degree and clinical TNM stage. Kaplan‐Meier analysis showed that patients with ESCC having low lncRNA HCG22 expression in ESCC tissues had considerably shorter overall survival compared with patients with ESCC having high lncRNA HCG22 expression. Following Transwell assays confirmed the migratory role of lncRNA HCG22 in ESCC cells. In conclusion, lncRNA HCG22 was downregulated in ESCC tissues and can be a migration inhibitor of ESCC cells, and SPINK7 and ADAMTS12 are promising to be the regulatory targets of lncRNA HCG22. Esophageal cancer is one of the most lethal malignancies in the world. But the altered long noncoding RNAs (lncRNAs) in esophageal squamous cell carcinoma (ESCC) tissues require a deeper excavation, and the regulatory mechanisms are barely discussed. In this study, we com