miR-21 expression predicts prognosis in hepatocellular carcinoma

Wang, Wenyao; Zhang, Hongfei; Wang, Lei; Ma, Yanpeng; Gao, Fei; Zhang, Shaojun; Wang, Lichao

doi:10.1016/j.clinre.2014.07.001

Cited by 34 publications

(27 citation statements)

References 21 publications

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“…We also noted increased AGO association and target binding in tumors for oncogenic miRNAs such as miR-21 (Figure 3A and S4B) (Jiang et al, 2008; Wang et al, 2014), highlighting the multifaceted nature of miRNA perturbation in this cancer. Global loss of miR-122 or gain of miR-21 binding in HCCs was likewise recapitulated in coding exons, introns, and 5’UTRs (Figure 3B).…”

Section: Resultsmentioning

confidence: 75%

Argonaute CLIP Defines a Deregulated miR-122-Bound Transcriptome that Correlates with Patient Survival in Human Liver Cancer

et al. 2017

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Summary MicroRNA-122, an abundant and conserved liver-specific miRNA, regulates hepatic metabolism and functions as a tumor suppressor, yet systematic and direct biochemical elucidation of the miR-122 target network remains incomplete. To this end, we performed Argonaute crosslinking immunoprecipitation (Ago-CLIP) sequencing in miR-122 knockout and control mouse livers, as well as in matched human hepatocellular carcinoma (HCC) and benign liver tissue to identify miRNA target sites transcriptome-wide in two species. We observed a majority of miR-122 binding on 3’-UTRs and coding exons followed by extensive binding to other genic and non-genic sites. Motif analysis of miR-122 dependent binding revealed a G-bulged motif in addition to canonical motifs. A large number of miR-122 targets were found to be species-specific. Upregulation of several common mouse and human targets, most notably BCL9, predicted survival in HCC patients. These results broadly define the molecular consequences of miR-122 downregulation in hepatocellular carcinoma.

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Section: Resultsmentioning

confidence: 75%

Argonaute CLIP Defines a Deregulated miR-122-Bound Transcriptome that Correlates with Patient Survival in Human Liver Cancer

et al. 2017

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“…On the other hand, miR-155-5p, miR-206, miR-21-5p and miR-212-3p could be recognized as biomarkers for HCC prognosis in tissues. The expression levels of miR-155-5p and miR-21-5p were up-regulated whereas others were down-regulated45464748. Circulating miR-122-5p and miR-16-5p could be used as putative biomarkers for HCC.…”

Section: Resultsmentioning

confidence: 96%

“…miR-101-3p, miR-106-5p, miR-17-5p, miR-18b-5p, miR-21-5p, miR-25-3p and miR-331-3p) and low expression of seven miRNAs ( i.e. miR-125a-5p, miR-128-3p, miR-188-5p, miR-206, miR-212-3p, miR-424-5p and miR-744-5p) were outstandingly correlated with limitless replicative potential and could provide positive prognostic values for HCC3846474852566465697073747687. Four prognostic circulating miRNAs associated with proliferation and limitless replicative potential, including miR-101-3p, miR-122-5p, miR-21-5p and miR-331-3p, were reported up-regulated in HCC patients38566177.…”

Section: Resultsmentioning

confidence: 97%

“…In tissues, with regard to up-regulated microRNAs in HCC tissues, highly expression of miR-106b-5p, miR-155-5p, miR-17-5p, miR-182-5p, miR-183-5p, miR-18b-5p, miR-21-5p, miR-25-3p, miR-331-3p, miR-9-5p and miR-96-5p were significantly correlated with invasion and metastasis454752566465666768697071. The expression level of miR-1269a in HCC patients without portal vein tumor embolus was reduced72.…”

Section: Resultsmentioning

confidence: 98%

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Biomarker MicroRNAs for Diagnosis, Prognosis and Treatment of Hepatocellular Carcinoma: A Functional Survey and Comparison

Shen

Lin

Yuan

et al. 2016

Sci Rep

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Hepatocellular Carcinoma (HCC) is one of the most common malignant tumors with high incidence and mortality rate. Precision and effective biomarkers are therefore urgently needed for the early diagnosis and prognostic estimation. MicroRNAs (miRNAs) are important regulators which play functions in various cellular processes and biological activities. Accumulating evidence indicated that the abnormal expression of miRNAs are closely associated with HCC initiation and progression. Recently, many biomarker miRNAs for HCC have been identified from blood or tissues samples, however, the universality and specificity on clinicopathological features of them are less investigated. In this review, we comprehensively surveyed and compared the diagnostic, prognostic, and therapeutic roles of HCC biomarker miRNAs in blood and tissues based on the cancer hallmarks, etiological factors as well as ethnic groups, which will be helpful to the understanding of the pathogenesis of biomarker miRNAs in HCC development and further provide accurate clinical decisions for HCC diagnosis and treatment.

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“…When detected early, HCC is treatable by surgical resection or transplantation, yet most patients present with advanced disease and have limited treatment options due to lack of effective therapies. Genomic profiling has identified a number of microRNAs that are dysregulated in HCC, including miR-21 (18,19). However, the precise contribution of miR-21 to the maintenance of oncogenic phenotype in HCC has not been fully established.…”

Section: Introductionmentioning

confidence: 99%

Anti–miR-21 Suppresses Hepatocellular Carcinoma Growth via Broad Transcriptional Network Deregulation

Wagenaar

Zabludoff

Ahn

et al. 2015

Molecular Cancer Research

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Hepatocellular carcinoma (HCC) remains a significant clinical challenge with few therapeutic options available to cancer patients. MicroRNA 21-5p (miR-21) has been shown to be upregulated in HCC, but the contribution of this oncomiR to the maintenance of tumorigenic phenotype in liver cancer remains poorly understood. We have developed potent and specific singlestranded oligonucleotide inhibitors of miR-21 (anti-miRNAs) and used them to interrogate dependency on miR-21 in a panel of liver cancer cell lines. Treatment with anti-miR-21, but not with a mismatch control anti-miRNA, resulted in significant derepression of direct targets of miR-21 and led to loss of viability in the majority of HCC cell lines tested. Robust induction of caspase activity, apoptosis, and necrosis was noted in anti-miR-21-treated HCC cells. Furthermore, ablation of miR-21 activity resulted in inhibition of HCC cell migration and suppression of clonogenic growth. To better understand the consequences of miR-21 suppression, global gene expression profiling was performed on anti-miR-21-treated liver cancer cells, which revealed striking enrichment in miR-21 target genes and deregulation of multiple growth-promoting pathways. Finally, in vivo dependency on miR-21 was observed in two separate HCC tumor xenograft models. In summary, these data establish a clear role for miR-21 in the maintenance of tumorigenic phenotype in HCC in vitro and in vivo.Implications: miR-21 is important for the maintenance of the tumorigenic phenotype of HCC and represents a target for pharmacologic intervention.

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miR-21 expression predicts prognosis in hepatocellular carcinoma

Cited by 34 publications

References 21 publications

Argonaute CLIP Defines a Deregulated miR-122-Bound Transcriptome that Correlates with Patient Survival in Human Liver Cancer

Argonaute CLIP Defines a Deregulated miR-122-Bound Transcriptome that Correlates with Patient Survival in Human Liver Cancer

Biomarker MicroRNAs for Diagnosis, Prognosis and Treatment of Hepatocellular Carcinoma: A Functional Survey and Comparison

Anti–miR-21 Suppresses Hepatocellular Carcinoma Growth via Broad Transcriptional Network Deregulation

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