Selecting molecular therapeutic drug targets based on the expression profiles of intrahepatic cholangiocarcinomas and miRNA-mRNA regulatory networks

Sun, Boshi; Xie, Changming; Zheng, Tongsen; Yin, Dalong; Wang, Jiabei; Liang, Yingjian; Li, Yuejin; Yang, Guangchao; Shi, Huawen; Pei, Tiemin; Han, Jing; Liu, Lianxin

doi:10.3892/or.2015.4330

Cited by 3 publications

(2 citation statements)

References 22 publications

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“…First, miR-146a inhibits tumor growth and metastasis by mediating various molecule activities [ 21 , 22 ] ; second, miR-146a increases the sensitivity of chemotherapy, radiotherapy, and targeted therapy, decreasing recurrence of ICC patients. [ 29 – 32 ]…”

Section: Discussionmentioning

confidence: 99%

Both plasma and tumor tissue miR-146a high expression correlates with prolonged overall survival of surgical patients with intrahepatic cholangiocarcinoma

Zhang

Zheng²,

Li³

et al. 2017

Medicine

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The purpose of this study was to investigate the association of tumor tissue and plasma miR-146a/b expressions with the clinicopathological properties and overall survival (OS) in surgical patients with intrahepatic cholangiocarcinomas (ICC).Eighty-seven patients with ICC were enrolled. Tumor tissue and plasma sample were collected and miR-146a/b expressions were assessed by quantitative polymerase chain reaction (qPCR). The median follow-up duration was 31 months, and the last follow-up date was January 2017.miR-146a (P < .001) and miR-146b (P = .006) expressions in tumor tissue were positively associated with that in plasma. Tissue miR-146a was negatively correlated with age (P = .036), poor differentiation (P = .020), N stage (P = .020), and TNM stage (P = .007), as well as ECOG performance (P = .008), whereas plasma miR-146a was inversely associated with N stage (P = .003), TNM stage (P = .003), and ECOG performance (P = .011). Moreover, tissue miR-146b was negatively correlated with gender (P = .043) and T stage (P = .047). Kaplan-Meier curves suggested that high expression of tissue miR-146a (P < .001) and plasma miR-146a (P = .029) were correlated with prolonged OS. Nevertheless, no association of miR-146b expression in tumor tissue (P = .187) and plasma (P = .336) with OS was discovered. Univariate analysis indicated that both tissue miR-146a (P < .001) and plasma miR-146a (P = .035) could predict better OS, whereas multivariate analysis revealed that only tissue miR-146a (P = .001) high expression was an independent factor for prolonged OS.Both plasma and tissue miR-146a expression correlated with favorable OS, whereas only tissue miR-146a was an independent prognostic biomarker in surgical patients with ICC.

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Section: Discussionmentioning

confidence: 99%

Both plasma and tumor tissue miR-146a high expression correlates with prolonged overall survival of surgical patients with intrahepatic cholangiocarcinoma

Zhang

Zheng²,

Li³

et al. 2017

Medicine

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show abstract

“…miRNAs may induce RNA-silencing and regulate gene expression at the post-transcriptional stage (27,28). The dysregulation of miRNA may result in numerous diseases, including ICC (29–31). The present study identified DEMs in ICC samples compared with healthy liver tissues samples, and the screening of DEM target genes was conducted using the TargetScan database.…”

Section: Discussionmentioning

confidence: 99%

Identification of biomarkers of intrahepatic cholangiocarcinoma via integrated analysis of mRNA and miRNA microarray data

Chang

Liu

et al. 2017

Molecular Medicine Reports

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The present study aimed to identify potential therapeutic targets of intrahepatic cholangiocarcinoma (ICC) via integrated analysis of gene (transcript version) and microRNA (miRNA/miR) expression. The miRNA microarray dataset GSE32957 contained miRNA expression data from 16 ICC, 7 mixed type of combined hepatocellular-cholangiocarcinoma (CHC), 2 hepatic adenoma, 3 focal nodular hyperplasia (FNH) and 5 healthy liver tissue samples, and 2 cholangiocarcinoma cell lines. In addition, the mRNA microarray dataset GSE32879 contained mRNA expression data from 16 ICC, 7 CHC, 2 hepatic adenoma, 5 FNH and 7 healthy liver tissue samples. The datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and miRNAs (DEMs) in ICC samples compared with healthy liver tissues were identified via the limma package, following data preprocessing. Genes that exhibited alternative splicing (AS) in ICC samples were identified via AltAnalyze software. Functional enrichment analysis of DEGs was performed using the Database for Annotation, Visualization and Integrated Analysis. Target genes of DEMs were identified using the TargetScan database. The regulatory association between DEMs and any overlaps among DEGs, alternative splicing genes (ASGs) and target genes of DEMs were retrieved, and a network was visualized using the Cytoscape software. A total of 2,327 DEGs, 70 DEMs and 623 ASGs were obtained. Functional enrichment analysis indicated that DEGs were primarily enriched in biological processes and pathways associated with cell activity or the immune system. A total of 63 overlaps were obtained among DEGs, ASGs and target genes of DEMs, and a regulation network that contained 243 miRNA-gene regulation pairs was constructed between these overlaps and DEMs. The overlapped genes, including sprouty-related EVH1 domain containing 1, protein phosphate 1 regulatory subunit 12A, chromosome 20 open reading frame 194, and DEMs, including hsa-miR-96, hsa-miR-1 and hsa-miR-25, may be potential therapeutic targets for the future treatment of ICC.

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miR-503-3p promotes epithelial–mesenchymal transition in breast cancer by directly targeting SMAD2 and E-cadherin

Zhao

Fan

Jiang

et al. 2017

Journal of Genetics and Genomics

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Selecting molecular therapeutic drug targets based on the expression profiles of intrahepatic cholangiocarcinomas and miRNA-mRNA regulatory networks

Cited by 3 publications

References 22 publications

Both plasma and tumor tissue miR-146a high expression correlates with prolonged overall survival of surgical patients with intrahepatic cholangiocarcinoma

Both plasma and tumor tissue miR-146a high expression correlates with prolonged overall survival of surgical patients with intrahepatic cholangiocarcinoma

Identification of biomarkers of intrahepatic cholangiocarcinoma via integrated analysis of mRNA and miRNA microarray data

miR-503-3p promotes epithelial–mesenchymal transition in breast cancer by directly targeting SMAD2 and E-cadherin

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