Repression of MicroRNA‐30e by Hepatitis C Virus Enhances Fatty Acid Synthesis

Sasaki, Reina; Sur, Subhayan; Cheng, Qi; Steele, Robert; Ray, Ratna B.

doi:10.1002/hep4.1362

Cited by 9 publications

(8 citation statements)

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“…( 25,40‐42 ) Furthermore, HCV‐induced lipogenesis contributes to the increased accumulation of LDs in cells, which facilitates virus assembly and secretion. ( 16,43 ) In this study, we showed that HCV RNA replication was significantly down‐regulated in Linc‐Pint overexpression. On the other hand, Linc‐Pint overexpression significantly reduced the de novo lipogenesis and LD accumulation in hepatocytes.…”

Section: Discussionmentioning

confidence: 61%

Inhibition of Long Noncoding RNA Linc‐Pint by Hepatitis C Virus in Infected Hepatocytes Enhances Lipogenesis

et al. 2021

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BaCKgRoUND aND aIMS: HCV often causes chronic infection in liver, cirrhosis, and, in some instances, HCC. HCV encodes several factors' those impair host genes for establishment of chronic infection. The long noncoding RNAs (lncRNAs) display diverse effects on biological regulations. However, their role in virus replication and underlying diseases is poorly understood. In this study, we have shown that HCV exploits lncRNA long intergenic nonprotein-coding RNA, p53 induced transcript (Linc-Pint) in hepatocytes for enhancement of lipogenesis. appRoaCH aND ReSUltS: We identified a lncRNA, Linc-Pint, which is significantly down-regulated in HCV-replicating hepatocytes and liver specimens from HCV infected patients. Using RNA pull-down proteomics, we identified serine/arginine protein specific kinase 2 (SRPK2) as an interacting partner of Linc-Pint. A subsequent study demonstrated that overexpression of Linc-Pint inhibits the expression of lipogenesis-related genes, such as fatty acid synthase and ATP-citrate lyase. We also observed that Linc-Pint significantly inhibits HCV replication. Furthermore, HCV-mediated enhanced lipogenesis can be controlled by exogenous Linc-Pint expression. Together, our results suggested that HCV-mediated down-regulation of Linc-Pint enhances lipogenesis favoring virus replication and liver disease progression. CoNClUSIoNS:We have shown that SRPK2 is a direct target of Linc-Pint and that depletion of SRPK2 inhibits lipogenesis. Our study contributes to the mechanistic understanding of the role of Linc-Pint in HCV-associated liver pathogenesis. (Hepatology 2021;74:41-54).

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Section: Discussionmentioning

confidence: 61%

Inhibition of Long Noncoding RNA Linc‐Pint by Hepatitis C Virus in Infected Hepatocytes Enhances Lipogenesis

et al. 2021

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“…The role of miR-30e in HCC development is thought to be through enhancement of autophagy leading to the development of HCC [25]. Recent studies have shown that miR-30e regulates the genes ATG5 and ATG12 which control the autophagy process [26]. Moreover, HOXA1, which has been recognized as a new miR-30e target, plays significant roles in regulating cell proliferation, carcinogenesis and metastasis [27].…”

Section: Resultsmentioning

confidence: 99%

MicroRNA-30e and MicroRNA-223 Expression for Early Diagnosis of Hepatocellular Carcinoma Associated with Hepatitis C Virus

Youssef

Bastawy

Montasser

et al. 2020

ammr

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Background. The goals of this study were to elucidate the use of the expression of microRNA-30e (miR-30e) and microRNA-223 (miR-223) as diagnostic biomarkers for early diagnosis of hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) infection. Methods. The study included three groups, the first group included thirty patients with HCC associated with HCV, the second group included thirty patients with cirrhosis with HCV and the third group included thirty healthy control subjects. Blood samples were obtained for determination of serum expression of miR-30e and miR-223 by real time polymerase chain reaction. Results. There was significant decrease of miR-30e of expression in patients with HCC (0.16 ± 0.1) compared to both patients with cirrhosis (0.4 ± 0.2, P<0.01) and healthy control subjects (1.2 ± 0.4, P<0.001). There was also significant reduction of miR-223 expression levels in patients with HCC (0.2 ± 0.1) compared to patients with cirrhosis (0.5 ± 0.2, P<0.01) and healthy control subjects (1.0 ± 0.1, P<0.001). There was also significant decrease of miR-30e expression in late stage versus early stage of HCC (0.1 ± 0.0 vs. 0.22 ± 0.1, P<0.001), while there was no significant difference of alpha-fetoprotein (AFP) between patients with late and early HCC. Also, values of miR-223 had significantly reduced levels in late HCC compared to its expression values in early HCC (0.1± 0.0 vs. 0.23 ± 0.2, P<001). Conclusion. There was significant reduction of expression of miR-30e and miR-223 in serum of HCC patients compared to either patients with cirrhosis or healthy subjects. These results show that the combined use of both biomarkers had better sensitivity in the diagnosis of HCC compared to AFP.

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“…Overexpression of miR-30e decreased the lipid synthesis-related proteins SREBP-1c and FASN in hepatocytes. It could also inhibit autophagy activation in HCV-infected hepatocytes [15]. In addition, it was also found that miR-30e could take part in HBVinduced liver brosis progression by targeting P4HA2 [16].…”

Section: Discussionmentioning

confidence: 99%

Identification of a potential miRNA-mRNA regulatory network associated with the pathogenesis of cholestatic liver diseases

Song

Geng

et al. 2022

Preprint

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Background Cholestatic liver diseases (CLDs), including primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), are common digestive diseases that may lead to liver fibrosis, cirrhosis, or even liver failure. However, ursodeoxycholic acid (UDCA), as the first-line drug therapy for PBC, achieves poor results among nearly half of patients. Furthermore, there are few effective ways to cure diseases other than liver transplantation at present. Therefore, it is essential to further explore the disease mechanism in order to find new therapeutic targets. Methods Gene Expression Omnibus (GEO) database (GSE159676) was used to screen differentially expressed hepatic miRNAs between PBC vs. control and PSC vs. control samples, and their interaction was considered as common miRNAs driving CLDs. A miRNA-mRNA network was then constructed based on predicted miRNA-targeted mRNAs. Then enrichment analysis was performed and protein-protein interaction (PPI) networks were constructed. In addition, these DEGs were also validated in models of cholestatic liver injury induced by α -isothiocyanate (ANIT) and bile duct ligation (BDL). Furthermore, the role of hub genes in cholestasis progression, UDCA response, and disease diagnosis were analyzed in GSE166867, GSE79850 and GSE119600, respectively. Results A total of 6 miRNAs and 437 mRNAs were identified as potential mediators in the pathophysiological processes of CLDs. Among them, 8 hub genes were identified (PTPRC, TYROBP, LCP2, RAC2, SYK, TLR2, CD53, and LAPTM5). The functional analysis confirmed that the molecular mechanism was strongly associated with Fc epsilon RI signaling pathway. Combining bioinformatics analysis with animal experimental results, miR-30e and miR-107 were the most significant DE-miRNAs. Additionally, activation of the 8 hub genes was observed in both ANIT-induced cholestasis model and time-course BDL model. Besides, an elevated hepatic SYK level was found in patients with UDCA inefficiency, and SYK in the blood may be an underlying diagnostic indicator for CLDs. Conclusions The present study constructed a miRNA-mRNA network of cholestatic liver diseases, and uncovered that the miR-30e, miR-107 and 8 hub genes could be involved in the pathogenesis of CLDs, providing potential therapeutic targets in CLDs.

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Repression of MicroRNA‐30e by Hepatitis C Virus Enhances Fatty Acid Synthesis

Cited by 9 publications

References 50 publications

Inhibition of Long Noncoding RNA Linc‐Pint by Hepatitis C Virus in Infected Hepatocytes Enhances Lipogenesis

Inhibition of Long Noncoding RNA Linc‐Pint by Hepatitis C Virus in Infected Hepatocytes Enhances Lipogenesis

MicroRNA-30e and MicroRNA-223 Expression for Early Diagnosis of Hepatocellular Carcinoma Associated with Hepatitis C Virus

Identification of a potential miRNA-mRNA regulatory network associated with the pathogenesis of cholestatic liver diseases

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