Clinical significance and potential of hepatic microRNA-122 expression in hepatitis C

Morita, Kazutoyo; Taketomi, Akinobu; Shirabe, Ken; Umeda, Kenji; Kuwabara, Hiroto; Ninomiya, Mizuki; Uchiyama, Hideaki; Soejima, Yuji; Maehara, Yoshihiko

doi:10.1111/j.1478-3231.2010.02433.x

Cited by 97 publications

(99 citation statements)

References 38 publications

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“…Our data confirmed that serum miR-122 level positively correlated with hepatic miR-122 expression, hepatic HAI score, and serum ALT levels in patients with CHC, suggesting a positive correlation with hepatic necroinflammation as previously reported (22,23,25). Therefore, serum miR-122 level could reflect hepatic miR-122 expression.…”

Section: Discussionsupporting

confidence: 91%

Serum microRNA-122 level correlates with virologic responses to pegylated interferon therapy in chronic hepatitis C

Liu

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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MicroRNA-122 (miR-122) facilitates hepatitis C virus replication in vitro. Serum miR-122 has been implicated as a biomarker for various liver diseases; however, its role in chronic hepatitis C remains unclear. To address this issue, 126 patients with chronic hepatitis C who completed pegylated IFN plus ribavirin therapy with sustained virologic response (SVR) or nonresponse (NR) were retrospectively included, and their pretreatment clinical profiles and treatment responses were collected. Serum miR-122 was quantified before and during treatment. Another 51 patients in SVR and NR groups were prospectively enrolled for validation. Serum miR-122 was found to be a surrogate for hepatic miR-122 and positively correlated with hepatic necroinflammation. Patients who showed complete early virologic response and SVR had significantly higher pretreatment serum miR-122 levels than those with NR (P = 0.001 and P = 0.008, respectively), especially in subgroups of patients with hepatitis C virus genotype 2 and IL-28B rs8099917 TT genotype. Patients with IL-28B TT genotype had significantly better treatment responses and higher pretreatment serum miR-122 level than those with GT or GG genotypes. Univariate analysis showed that pretreatment body mass index, γ-glutamyl transpeptidase, triglyceride, IL-28B TT genotype, and serum miR-122 are predictors for SVR. Multivariate analysis specifically in IL-28B TT genotype demonstrated that pretreatment serum miR-122 independently predicted SVR. The validation cohort confirmed a significantly greater pretreatment serum miR-122 level in patients with SVR compared with NR (P = 0.025). In conclusion, serum miR-122 may serve as a surrogate of hepatic miR-122, and a higher pretreatment serum miR-122 level can help predict virologic responses to pegylated IFN plus ribavirin therapy.

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Section: Discussionsupporting

confidence: 91%

Serum microRNA-122 level correlates with virologic responses to pegylated interferon therapy in chronic hepatitis C

Liu

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…In addition, miR-122 levels were shown to be negatively correlated with the expression of IRGs, indicating that CHC subjects with PNR have both lower pretreatment miR-122 levels and higher IRG levels. Another puzzling feature is that hepatic miR-122 expression in CHC patients was shown unrelated with the hepatic HCV load, and was inversely correlated with the severity of functional and histopathological liver damage (Morita et al, 2011). This paper therefore states that miR-122 by itself is not a critical molecular target for HCV therapy.…”

Section: Mir-122 In Hcv Infectionmentioning

confidence: 92%

MiR-122 in hepatic function and liver diseases

et al. 2012

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“…(10) The expression levels of microRNA-18a (miR-18a) and microRNA-199a-5p (miR-199a-5p) were quantified by the relative standard curve method using a control sample (histopathologically NL sample from a patient with a metastatic liver tumor) and normalized according to the level of expression of RNU6B.…”

Section: Quantitative Reverse Transcription-polymerase Chain Reactionmentioning

confidence: 99%

“…(7)(8)(9) MiRNAs are implicated in many biological processes and diverse diseases, such as viral infections and cancers. (10)(11)(12)(13) Recently, metastasis-related miRNAs in HCC were analyzed by comparing primary hepatocellular carcinoma (T) and noncancerous liver (N) (14) or T, adjacent venous tumor thrombus, and N. (15) In HCC, cancer metastasis is very complex with multiple steps, including local invasion, intravasation, survival in the circulation, extravasation, and colonization, which is accompanied by the accumulation of genetic and epigenetic alterations. (16) Furthermore, metastatic clones are derived from only a few clones in the genetically heterogeneous primary cancer.…”

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confidence: 99%

Relevance of microRNA‐18a and microRNA‐199a‐5p to hepatocellular carcinoma recurrence after living donor liver transplantation

et al. 2016

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There are few reports about recurrence-related microRNAs (miRNAs) after liver transplantation (LT) for hepatocellular carcinoma (HCC). The purpose of this study was to identify novel recurrence-related miRNAs after living donor liver transplantation (LDLT) for HCC. First, we performed microarray analyses of samples from a liver with primary HCC, a liver that was noncancerous, and a liver that had recurrence-metastasis from 3 patients with posttransplant recurrence. Then we selected miRNAs with consistently altered expression in both primary HCC and recurrence as potential candidates of recurrence-related miRNAs. Expression of the miRNAs in HCC and noncancerous livers was assessed in 70 HCC patients who underwent LDLT. The target genes regulated by the recurrence-related miRNAs were identified. MicroRNA-18a (miR-18a) expression was increased, and microRNA-199a-5p (miR-199a-5p) expression was decreased in both primary HCC and recurrence. Increased miR-18a expression correlated with high levels of tumor markers, large tumor size, and a high recurrence rate. Decreased miR-199a-5p expression correlated with high levels of tumor markers, portal venous invasion, and a high recurrence rate. In HCC cells, miR-18a regulated the expression of tumor necrosis factor alpha-induced protein 3 (TNFAIP3), and miR-199a-5p regulated the expression of hypoxia-inducible factor 1 alpha (HIF1A), vascular endothelial growth factor A (VEGFA), insulin-like growth factor 1 receptor, and insulin-like growth factor 2. In conclusion, increased miR-18a levels and decreased miR-199a-5p levels are relevant to HCC recurrence after LDLT. MiR-18a and miR-199a-5p could be novel therapeutic targets of recurrent HCC after LDLT.Liver Transplantation 22 665-676 2016 AASLD.Received August 31, 2015; accepted December 9, 2015.Hepatocellular carcinoma (HCC) is the most frequent cancer of the liver and the third most common cause of cancer deaths worldwide.(1) Curative treatment is limited to hepatic resection and liver transplantation (LT). However, the overall cumulative recurrence rate after hepatic resection is approximately 80% at 5 years.(2) Among various recurrent patterns of HCC, the prognosis of extrahepatic recurrence-metastasis (M) is much poorer than that of intrahepatic metastasis and multicentric recurrence. (3)(4)(5) LT can overcome the problems of intrahepatic metastasis and multicentric recurrence theoretically. However, the recurrence of HCC after LT is a critical problem to be solved because the outcomes of patients with HCC recurrence after LT are extremely poor. (6) Abbreviations: AFP, alpha-fetoprotein; DCP, des-gamma-carboxyprothrombin; DDLT, deceased donor liver transplantation; HBsAg, hepatitis B surface antigen; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HIF1A, hypoxia-inducible factor 1 alpha; IGF1R, insulin-like growth factor 1 receptor; IGF2, insulin-like growth factor 2; LDLT, living donor liver transplantation; LT, liver transplantation; M, recurrence-metastasis; miR-18a, microRNA-18a; miR-199a-5p, microRNA-199a-5p;...

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Clinical significance and potential of hepatic microRNA-122 expression in hepatitis C

Cited by 97 publications

References 38 publications

Serum microRNA-122 level correlates with virologic responses to pegylated interferon therapy in chronic hepatitis C

Serum microRNA-122 level correlates with virologic responses to pegylated interferon therapy in chronic hepatitis C

MiR-122 in hepatic function and liver diseases

Relevance of microRNA‐18a and microRNA‐199a‐5p to hepatocellular carcinoma recurrence after living donor liver transplantation

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