MicroRNA-21 suppresses PTEN and hSulf-1 expression and promotes hepatocellular carcinoma progression through AKT/ERK pathways

Bao, Linlin; Yan, Yan; Xu, Cuilian; Ji, Weidan; Shen, Shuwen; Xu, Gaoya; Zeng, Yong; Sun, Bin; Qian, Haihua; Chen, Lei; Wu, Mengchao; Su, Changqing; Chen, Jie

doi:10.1016/j.canlet.2013.05.007

Cited by 162 publications

(128 citation statements)

References 39 publications

Supporting

Mentioning

123

Contrasting

Order By: Relevance

“…PTEN is an important inhibitory protein of the PI3K/serine threonine protein kinase (AKT) pathway. Therefore, the consequence of the inhibition of PTEN by miR21 is the activation of the PI3K/AKT pathway, which promotes cancer cell proliferation and metastasis (28). miR221/222 acts on many key tumor suppressors, including Bmf (29) (35).…”

Section: Discussionmentioning

confidence: 99%

“…The decreased expression and the loss of function of PTEN and hSulf-1 can upregulate AKT/ERK activity, thereby enhancing the proliferation, invasion, and migration ability of HCC cells. Inhibition of miR21 function by miR21 inhibitor can inhibit the proliferation and metastasis capacity of HCC cells (28). However, compared with normal cells, there are many differentially expressed miRNAs in cancer cells, and their functions are complex.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

An Artificially Designed Interfering lncRNA Expressed by Oncolytic Adenovirus Competitively Consumes OncomiRs to Exert Antitumor Efficacy in Hepatocellular Carcinoma

Sun

et al. 2016

Molecular Cancer Therapeutics

Self Cite

View full text Add to dashboard Cite

Endogenous miRNAs, especially oncogenic miRNAs (OncomiR), have been molecular targets for cancer therapy. We generated an artificially designed interfering long noncoding RNA (lncRNAi), which contains the sequences that can complementarily bind to multiple OncomiRs and is expressed by cancer-selectively replicating adenovirus. The adenovirus-expressed lncRNAi with high levels in hepatocellular carcinoma (HCC) cells competes with OncomiR target genes to bind to and consume OncomiRs, thereby achieving the targeted anti-HCC efficacy. With the targeting replication of adenovirus in HCC cells, lncRNAi was highly expressed and resulted in decreased abilities of proliferation, migration, and invasion, induced cell-cycle changes and apoptosis, and markedly changed the cellular mRNA and miRNA expression profiles in HCC cells. The optimal antitumor effect was also demonstrated on HCC cell line xenograft models and HCC patient-derived xenograft (PDX) tumor models in nude mice. This strategy has established a technology platform with a reliable therapeutic effect for HCC therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

An Artificially Designed Interfering lncRNA Expressed by Oncolytic Adenovirus Competitively Consumes OncomiRs to Exert Antitumor Efficacy in Hepatocellular Carcinoma

Sun

et al. 2016

Molecular Cancer Therapeutics

Self Cite

View full text Add to dashboard Cite

show abstract

“…Among the upregulated miRNAs, miR-21-5p was previously reported to be enhanced by HCV in both Huh7-derived cells and liver tissues (47)(48)(49). Interestingly, miR-21-5p appears to be highly expressed in HCC tumors and cell lines, in which it was shown to enhance cell proliferation, migration, and invasion (50,51). Aiming to identify additional virusmediated alterations of miRNA patterns that may be linked to liver disease and hepatocarcinogenesis, we chose to focus our investigation on miRNAs that were previously described to target genes associated with inflammation, fibrosis, and cancer development but have not yet been linked strongly to HCV-mediated hepatocyte injury (Table 2).…”

Section: Persistent Hcv Infection Induces the Upregulation Of Mir146amentioning

confidence: 99%

Hepatitis C Virus-Induced Upregulation of MicroRNA miR-146a-5p in Hepatocytes Promotes Viral Infection and Deregulates Metabolic Pathways Associated with Liver Disease Pathogenesis

Bandiera

Pernot

Saghire

et al. 2016

J Virol

View full text Add to dashboard Cite

Hepatitis C virus (HCV)-induced chronic liver disease is a leading cause of hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying HCC development following chronic HCV infection remain poorly understood. MicroRNAs (miRNAs) play an important role in homeostasis within the liver, and deregulation of miRNAs has been associated with liver disease, including HCC. While host miRNAs are essential for HCV replication, viral infection in turn appears to induce alterations of intrahepatic miRNA networks. Although the cross talk between HCV and liver cell miRNAs most likely contributes to liver disease pathogenesis, the functional involvement of miRNAs in HCV-driven hepatocyte injury and HCC remains elusive. Here we combined a hepatocyte-like cell-based model system, high-throughput small RNA sequencing, computational analysis, and functional studies to investigate HCV-miRNA interactions that may contribute to liver disease and HCC. Profiling analyses indicated that HCV infection differentially regulated the expression of 72 miRNAs by at least 2-fold, including miRNAs that were previously described to target genes associated with inflammation, fibrosis, and cancer development. Further investigation demonstrated that the miR-146a-5p level was consistently increased in HCV-infected hepatocyte-like cells and primary human hepatocytes, as well as in liver tissue from HCV-infected patients. Genomewide microarray and computational analyses indicated that miR-146a-5p overexpression modulates pathways that are related to liver disease and HCC development. Furthermore, we showed that miR-146a-5p has a positive impact on late steps of the viral replication cycle, thereby increasing HCV infection. Collectively, our data indicate that the HCV-induced increase in miR-146a-5p expression both promotes viral infection and is relevant for pathogenesis of liver disease. IMPORTANCEHCV is a leading cause of chronic liver disease and cancer. However, how HCV induces liver cancer remains poorly understood. There is accumulating evidence that a viral cure does not eliminate the risk for HCC development. Thus, there is an unmet medical need to develop novel approaches to predict and prevent virus-induced HCC. miRNA expression is known to be deregulated in liver disease and cancer. Furthermore, miRNAs are essential for HCV replication, and HCV infection alters miRNA expression. However, how miRNAs contribute to HCV-driven pathogenesis remains elusive. Here we show that HCV induces miRNAs that may contribute to liver injury and carcinogenesis. The miR-146a-5p level was consistently increased in different cell-based models of HCV infection and in HCV patient-derived liver tissue. Furthermore, miR-146a-5p increased HCV infection. Collectively, our data are relevant to understanding viral pathogenesis and may open perspectives for novel biomarkers and prevention of virus-induced liver disease and HCC. H epatitis C virus (HCV) infection is a leading cause of chronic liver disease and hepatocellular carcinoma (HCC) worldw...

show abstract

“…The oncosuppressor effect of SULF1 was confirmed by the recent observation that microRNA-21, a suppressor of PTEN and hSulf-1 expression, promotes HCC progression through the AKT/ERK pathways (13). It was hypothesized that the inhibition of histone deacetylase by SULF1 induces a rise in acetylated histone H4, which leads to inhibition of RAS/ERK and PI3K/AKT signaling (13) Figure 1B).…”

Section: Heparin-degrading Sulfatasesmentioning

confidence: 55%

Sulfatase 1: a new Jekyll and Hyde in hepatocellular carcinoma?

Pascale

Calvisi

Feo

2016

Transl. Gastroenterol. Hepatol.

View full text Add to dashboard Cite

MicroRNA-21 suppresses PTEN and hSulf-1 expression and promotes hepatocellular carcinoma progression through AKT/ERK pathways

Cited by 162 publications

References 39 publications

An Artificially Designed Interfering lncRNA Expressed by Oncolytic Adenovirus Competitively Consumes OncomiRs to Exert Antitumor Efficacy in Hepatocellular Carcinoma

An Artificially Designed Interfering lncRNA Expressed by Oncolytic Adenovirus Competitively Consumes OncomiRs to Exert Antitumor Efficacy in Hepatocellular Carcinoma

Hepatitis C Virus-Induced Upregulation of MicroRNA miR-146a-5p in Hepatocytes Promotes Viral Infection and Deregulates Metabolic Pathways Associated with Liver Disease Pathogenesis

Sulfatase 1: a new Jekyll and Hyde in hepatocellular carcinoma?

Contact Info

Product

Resources

About