HepatomiRNoma: The proposal of a new network of targets for diagnosis, prognosis and therapy in hepatocellular carcinoma

Bronte, F.; Bronte, Giuseppe; Fanale, Daniele; Caruso, Stefano; Bronte, Enrico; Bavetta, Maria Grazia; Fiorentino, Eugenio; Rolfo, Christian; Bazan, Viviana; Marco, V. Di; Russo, Antonio

doi:10.1016/j.critrevonc.2015.09.007

Cited by 31 publications

(23 citation statements)

References 119 publications

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“…Additionally, miR-221 also had a higher expression level in NSCLC [35]. Further researches give a conclusion that through the stimulation from staphylococcal nuclease domain-containing 1 (SND1), miR-221 could result in the overexpression of angiogenic factors like angiogenin and CXCL16 [36]. By using parallel measurement, a change in CDKN1B, CDKN1C, paralemmin-2, and CXCL12 levels was suggested as consistent with increased miR-221 activity in the same group.…”

Section: Discussionmentioning

confidence: 99%

Identification and interaction analysis of key genes and microRNAs in hepatocellular carcinoma by bioinformatics analysis

et al. 2017

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BackgroundHepatocellular carcinoma (HCC) is the most common liver malignancy worldwide. However, present studies of its multiple gene interaction and cellular pathways still could not explain the initiation and development of HCC perfectly. To find the key genes and miRNAs as well as their potential molecular mechanisms in HCC, microarray data GSE22058, GSE25097, and GSE57958 were analyzed.MethodsThe microarray datasets GSE22058, GSE25097, and GSE57958, including mRNA and miRNA profiles, were downloaded from the GEO database and were analyzed using GEO2R. Functional and pathway enrichment analyses were performed using the DAVID database, and the protein–protein interaction (PPI) network was constructed using the Cytoscape software. Finally, miRDB was applied to predict the targets of the differentially expressed miRNAs (DEMs).ResultsA total of 115 differentially expressed genes (DEGs) were found in HCC, including 52 up-regulated genes and 63 down-regulated genes. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses from DAVID showed that up-regulated genes were significantly enriched in chromosome segregation and cell division, while the down-regulated genes were mainly involved in complement activation, protein activation cascades, carboxylic acid metabolic processes, oxoacid metabolic processes, and the immune response. From the PPI network, the 18 nodes with the highest degree were screened as hub genes. Among them, ESR1 was found to have close interactions with FOXO1, CXCL12, and GNAO1. In addition, a total of 64 DEMs were identified, which included 58 up-regulated miRNAs and 6 down-regulated miRNAs. ESR1 was potentially targeted by five miRNAs, including hsa-mir-18a and hsa-mir-221.ConclusionsThe roles of DEMs like hsa-mir-221 in HCC through interactions with DEGs such as ESR1 and CXCL12 may provide new clues for the diagnosis and treatment of HCC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12957-017-1127-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Identification and interaction analysis of key genes and microRNAs in hepatocellular carcinoma by bioinformatics analysis

et al. 2017

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“…Inhibition of oncomiRs using antisense oligomers (antimiRs) has been shown as an evolving therapeutic strategy [6]. Previous studies have demonstrated their potential value in the clinical management of patients with HCC as some miRNAs may be used as prognostic or diagnostic markers as well as potential therapeutic targets [7, 8]. For instance, systemic administration of miR-26a, a miRNA that is normally expressed at high levels in normal liver but decreased in HCC cells, in a mouse model of HCC using adeno-associated virus (AAV) results in inhibition of cancer cell proliferation, induction of tumor-specific apoptosis, and dramatic protection from disease progression without toxicity [9].…”

Section: Discussionmentioning

confidence: 99%

Loss of miR-1258 contributes to carcinogenesis and progression of liver cancer through targeting CDC28 protein kinase regulatory subunit 1B

Wang

et al. 2016

Oncotarget

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Hepatocellular carcinoma (HCC) is the leading cause of cancer related death worldwide. The number of deaths is proportional to the global incidence, which highlights the aggressive tumor biology and lack of effective therapies. Dysregulation of microRNAs has been implicated in carcinogenesis and progression of liver cancer. Here, we identified that miR-1258 was significantly downregulated in HCC and associated with poor patients' survival. Overexpression of miR-1258 significantly inhibits liver cancer cell growth, proliferation and tumorigenicity through increasing cell cycle arrest in G0/G1 phase and promotes cell apoptosis. Interestingly, stable overexpression of miR-1258 suppresses cell migration, stemness and increases sensitivity of HCC cells to chemotherapy drug like doxorubicin. The CDC28 protein kinase regulatory subunit 1B (CKS1B) was identified as a functional downstream target of miR-1258. Re-expression of CKS1B overcomes miR-1258 induced apoptosis and increases stemness of HCC cells, suggesting that loss of miR-1258 contributes to carcinogenesis and progression of liver cancer through targeting CKS1B. Therefore, loss of miR-1258 may be a potential diagnostic and prognostic biomarker and blocking miR-1258-CKS1B axis is a potential therapeutic strategy in HCC.

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“…MiRNAs are involved in the regulation of a wide range of biological processes, such mechanisms of embryonic development, cell differentiation, apoptosis, cell growth control and regulation of metabolic processes [27–30]. Changes in miRNAs could be important in the development of BE and its progression [18, 31, 32].…”

Section: Discussionmentioning

confidence: 99%

Analysis of tissue and circulating microRNA expression during metaplastic transformation of the esophagus

et al. 2016

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Genetic changes involved in the metaplastic progression from squamous esophageal mucosa toward Barrett's metaplasia and adenocarcinoma are almost unknown. Several evidences suggest that some miRNAs are differentially expressed in Barrett's esophagus (BE) and esophageal adenocarcinoma. Among these, miR-143, miR-145, miR-194, miR-203, miR-205, miR-215 appear to have a key role in metaplasia and neoplastic progression. The aim of this study was to analyze deregulated miRNAs in serum and esophageal mucosal tissue biopsies to identify new biomarkers that could be associated with different stages of esophageal disease. Esophageal mucosal tissue biopsies and blood samples were collected and analyzed for BE diagnosis. Quantitative Real-time PCR was used to compare miRNA expression levels in serum and 60 disease/normal-paired tissues from 30 patients diagnosed with esophagitis, columnar-lined oesophagus (CLO) or BE. MiRNA expression analysis showed that miR-143, miR-145, miR-194 and miR-215 levels were significantly higher, while miR-203 and miR-205 were lower in BE tissues compared with their corresponding normal tissues. Esophageal mucosa analysis of patients with CLO and esophagitis showed that these miRNAs were similarly deregulated but to a lesser extent keeping the same trend and CLO appeared as intermediate step between esophagitis and BE. Analysis on circulating miRNA levels confirmed that miR-194 and miR-215 were significantly upregulated in both BE and CLO compared to esophagitis, while miR-143 was significantly upregulated only in the Barrett group. These findings suggest that miRNAs may be involved in neoplastic/metaplastic progression and miRNA analysis might be useful for progression risk prediction as well as for monitoring of BE/CLO patients.

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HepatomiRNoma: The proposal of a new network of targets for diagnosis, prognosis and therapy in hepatocellular carcinoma

Cited by 31 publications

References 119 publications

Identification and interaction analysis of key genes and microRNAs in hepatocellular carcinoma by bioinformatics analysis

Identification and interaction analysis of key genes and microRNAs in hepatocellular carcinoma by bioinformatics analysis

Loss of miR-1258 contributes to carcinogenesis and progression of liver cancer through targeting CDC28 protein kinase regulatory subunit 1B

Analysis of tissue and circulating microRNA expression during metaplastic transformation of the esophagus

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