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

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.

Li X ，Xiao X ，Chang R ，Zhang C ... -  《-》

Bioinformatics-based analysis of the lncRNA-miRNA-mRNA and TF regulatory networks reveals functional genes in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a 5-year survival rate unsatisfied malignancies. The study aimed to identify the novel diagnostic and prognostic targets for ESCC. Expression profiling (GSE89102, GSE97051, and GSE59973) data were downloaded from the GEO database. Then, differentially expressed (DE) lncRNAs, DEmiRNAs, and genes (DEGs) with P-values < 0.05, and |log2FC| ≥ 2, were identified using GEO2R. Functional enrichment analysis of miRNA-related mRNAs and lncRNA co-expressed mRNA was performed. LncRNA-miRNA-mRNA, protein-protein interaction of miRNA-related mRNAs and DEGs, co-expression, and transcription factors-hub genes network were constructed. The transcriptional data, the diagnostic and prognostic value of hub genes were estimated with ONCOMINE, receiver operating characteristic (ROC) analyses, and Kaplan-Meier plotter, respectively. Also, the expressions of hub genes were assessed through qPCR and Western blot assays. The CDK1, VEGFA, PRDM10, RUNX1, CDK6, HSP90AA1, MYC, EGR1, and SOX2 used as hub genes. And among them, PRDM10, RUNX1, and CDK6 predicted worse overall survival (OS) in ESCC patients. Our results showed that the hub genes were significantly up-regulated in ESCA primary tumor tissues and cell lines, and exhibited excellent diagnostic efficiency. These results suggest that the hub genes may server as potential targets for the diagnosis and treatment of ESCC.

Ye Z ，Fang J ，Wang Z ，Wang L ，Li B ，Liu T ，Wang Y ，Hua J ，Wang F ，Fu Z ... -  《-》

Transcriptome profiling of lncRNA and co-expression networks in esophageal squamous cell carcinoma by RNA sequencing.

Li Y ，Shi X ，Yang W ，Lu Z ，Wang P ，Chen Z ，He J ... -  《-》

Genome-wide analyses of long non-coding RNA expression profiles and functional network analysis in esophageal squamous cell carcinoma.

Ma J ，Xiao Y ，Tian B ，Chen S ，Zhang B ，Wu J ，Wu Z ，Li X ，Tang J ，Yang D ，Zhou Y ，Wang H ，Su M ，Wang W ... -  《Scientific Reports》

Long noncoding RNA lnc-ABCA12-3 promotes cell migration, invasion, and proliferation by regulating fibronectin 1 in esophageal squamous cell carcinoma.

Long noncoding RNAs (lncRNAs) have been shown to play important roles in human cancers, including esophageal squamous cell carcinoma (ESCC). We previously demonstrated that a novel lncRNA, lnc-ABCA12-3, was overexpressed in ESCC tissues. However, the exact function of lnc-ABCA12-3 is unknown. In the current study, we aimed to evaluate the expression of lnc-ABCA12-3 in ESCC and to explore the potential mechanism of lnc-ABCA12-3 in cell migration, invasion, and proliferation. We showed that lnc-ABCA12-3 was upregulated in ESCC tumor tissues and cell lines. The increased expression of lnc-ABCA12-3 was positively associated with advanced tumor-node-metastasis stages and poor prognosis. The knockdown of lnc-ABCA12-3 inhibited the cell migration, invasion, and proliferation abilities of KYSE-510 and Eca-109 cells. We also found that fibronectin 1 (FN1) was upregulated in ESCC tumor tissues. The expression of FN1 messenger RNA was positively correlated with the expression of lnc-ABCA12-3 in ESCC tumor tissues. After lnc-ABCA12-3 knockdown, the expression of FN1 was downregulated. In addition, the overexpression of FN1 restored the abilities of cell migration, invasion and proliferation in Eca-109 cells. Further studies indicated that lnc-ABCA12-3 acted as a competing endogenous RNA for miR-200b-3p to regulate FN1 expression. In conclusion, these results suggest that lnc-ABCA12-3 is a novel oncogene in tumorigenesis and that its high expression is related to a poor prognosis for patients with ESCC. lnc-ABCA12-3 promotes cell migration, invasion, and proliferation via the regulation of FN1 in ESCC. Our data suggest that lnc-ABCA12-3 might serve as a potential prognostic biomarker and therapeutic target for ESCC.

Ma J ，Xiao Y ，Tian B ，Chen S ，Zhang B ，Wu J ，Wu Z ，Li X ，Tang J ，Yang D ，Zhou Y ，Wang H ，Su M ，Wang W ... -  《-》