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

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

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Abstract

Background and aims: MicroRNAs are small non-coding RNA molecules that post-transcriptionally regulate gene expression. Liver-specific microRNA-122 (miR-122) has been shown to facilitate the replication of hepatitis C virus (HCV) in human hepatoma cells in vitro. However, the clinical significance of hepatic miR-122 on HCV in human body is unclear. Methods: Hepatic miR-122 expression was quantified using quantitative reverse-transcription polymerase chain reaction. We investigated the correlation between miR-122 expression and HCV load in liver samples from 185 patients seropositive for HCV antibody, including 151 patients seropositive for HCV RNA, and 31 patients seronegative for HCV RNA. Results: Although hepatic miR-122 expression was weakly and positively correlated with the serum HCV load (ρ=0.19, P<0.05), it was not correlated with the hepatic HCV load (ρ=-0.14, P=0.08). The absence of a correlation between miR-122 expression and hepatic HCV load was also confirmed after stratification of histopathological liver damage (inflammatory activity grades and fibrosis stages). Furthermore, hepatic miR-122 expression in patients seronegative for HCV RNA was significantly higher than that in patients seropositive for HCV RNA (P<0.0001). The level of hepatic miR-122 expression was inversely correlated with the severity of functional and histopathological liver damage (P<0.0001), serum transaminase levels (P<0.0005). Conclusions: Compared with in vitro findings, hepatic miR-122 expression is not correlated with HCV load in the human liver. Therefore, miR-122, by itself, is not a critical molecular target for HCV therapy. MiR-122 expression is inversely correlated with both functional and histopathological liver damage.

Original languageEnglish
Pages (from-to)474-484
Number of pages11
JournalLiver International
Volume31
Issue number4
DOIs
Publication statusPublished - Apr 1 2011

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Hepatitis C
MicroRNAs
Hepacivirus
Liver
RNA
Small Untranslated RNA
Hepatitis C Antibodies
Transaminases
Serum
Human Body
Reverse Transcription
Hepatocellular Carcinoma
Fibrosis

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Morita, K., Taketomi, A., Shirabe, K., Umeda, K., Kayashima, H., Ninomiya, M., ... Maehara, Y. (2011). Clinical significance and potential of hepatic microRNA-122 expression in hepatitis C. Liver International, 31(4), 474-484. https://doi.org/10.1111/j.1478-3231.2010.02433.x

Clinical significance and potential of hepatic microRNA-122 expression in hepatitis C. / Morita, Kazutoyo; Taketomi, Akinobu; Shirabe, Ken; Umeda, Kenji; Kayashima, Hiroto; Ninomiya, Mizuki; Uchiyama, Hideaki; Soejima, Yuji; Maehara, Yoshihiko.

In: Liver International, Vol. 31, No. 4, 01.04.2011, p. 474-484.

Research output: Contribution to journalArticle

Morita, K, Taketomi, A, Shirabe, K, Umeda, K, Kayashima, H, Ninomiya, M, Uchiyama, H, Soejima, Y & Maehara, Y 2011, 'Clinical significance and potential of hepatic microRNA-122 expression in hepatitis C', Liver International, vol. 31, no. 4, pp. 474-484. https://doi.org/10.1111/j.1478-3231.2010.02433.x
Morita K, Taketomi A, Shirabe K, Umeda K, Kayashima H, Ninomiya M et al. Clinical significance and potential of hepatic microRNA-122 expression in hepatitis C. Liver International. 2011 Apr 1;31(4):474-484. https://doi.org/10.1111/j.1478-3231.2010.02433.x
Morita, Kazutoyo ; Taketomi, Akinobu ; Shirabe, Ken ; Umeda, Kenji ; Kayashima, Hiroto ; Ninomiya, Mizuki ; Uchiyama, Hideaki ; Soejima, Yuji ; Maehara, Yoshihiko. / Clinical significance and potential of hepatic microRNA-122 expression in hepatitis C. In: Liver International. 2011 ; Vol. 31, No. 4. pp. 474-484.
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AU - Kayashima, Hiroto

AU - Ninomiya, Mizuki

AU - Uchiyama, Hideaki

AU - Soejima, Yuji

AU - Maehara, Yoshihiko

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N2 - Background and aims: MicroRNAs are small non-coding RNA molecules that post-transcriptionally regulate gene expression. Liver-specific microRNA-122 (miR-122) has been shown to facilitate the replication of hepatitis C virus (HCV) in human hepatoma cells in vitro. However, the clinical significance of hepatic miR-122 on HCV in human body is unclear. Methods: Hepatic miR-122 expression was quantified using quantitative reverse-transcription polymerase chain reaction. We investigated the correlation between miR-122 expression and HCV load in liver samples from 185 patients seropositive for HCV antibody, including 151 patients seropositive for HCV RNA, and 31 patients seronegative for HCV RNA. Results: Although hepatic miR-122 expression was weakly and positively correlated with the serum HCV load (ρ=0.19, P<0.05), it was not correlated with the hepatic HCV load (ρ=-0.14, P=0.08). The absence of a correlation between miR-122 expression and hepatic HCV load was also confirmed after stratification of histopathological liver damage (inflammatory activity grades and fibrosis stages). Furthermore, hepatic miR-122 expression in patients seronegative for HCV RNA was significantly higher than that in patients seropositive for HCV RNA (P<0.0001). The level of hepatic miR-122 expression was inversely correlated with the severity of functional and histopathological liver damage (P<0.0001), serum transaminase levels (P<0.0005). Conclusions: Compared with in vitro findings, hepatic miR-122 expression is not correlated with HCV load in the human liver. Therefore, miR-122, by itself, is not a critical molecular target for HCV therapy. MiR-122 expression is inversely correlated with both functional and histopathological liver damage.

AB - Background and aims: MicroRNAs are small non-coding RNA molecules that post-transcriptionally regulate gene expression. Liver-specific microRNA-122 (miR-122) has been shown to facilitate the replication of hepatitis C virus (HCV) in human hepatoma cells in vitro. However, the clinical significance of hepatic miR-122 on HCV in human body is unclear. Methods: Hepatic miR-122 expression was quantified using quantitative reverse-transcription polymerase chain reaction. We investigated the correlation between miR-122 expression and HCV load in liver samples from 185 patients seropositive for HCV antibody, including 151 patients seropositive for HCV RNA, and 31 patients seronegative for HCV RNA. Results: Although hepatic miR-122 expression was weakly and positively correlated with the serum HCV load (ρ=0.19, P<0.05), it was not correlated with the hepatic HCV load (ρ=-0.14, P=0.08). The absence of a correlation between miR-122 expression and hepatic HCV load was also confirmed after stratification of histopathological liver damage (inflammatory activity grades and fibrosis stages). Furthermore, hepatic miR-122 expression in patients seronegative for HCV RNA was significantly higher than that in patients seropositive for HCV RNA (P<0.0001). The level of hepatic miR-122 expression was inversely correlated with the severity of functional and histopathological liver damage (P<0.0001), serum transaminase levels (P<0.0005). Conclusions: Compared with in vitro findings, hepatic miR-122 expression is not correlated with HCV load in the human liver. Therefore, miR-122, by itself, is not a critical molecular target for HCV therapy. MiR-122 expression is inversely correlated with both functional and histopathological liver damage.

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