miR-122

miR-122 is a miRNA that is conserved among vertebrate species. miR-122 is not present in invertebrates, and no close paralogs of miR-122 have been detected.[1] miR-122 is highly expressed in the liver, where it has been implicated as a regulator of fatty-acid metabolism in mouse studies. Reduced miR-122 levels are associated with hepatocellular carcinoma. miR-122 also plays an important positive role in the regulation of hepatitis C virus replication.

mir-122 microRNA precursor
Identifiers
Symbolmir-122
RfamRF00684
miRBaseMI0000442
miRBase familyMIPF0000095
Other data
RNA typeGene; miRNA
Domain(s)Eukaryota
GOGO:0035195 GO:0035068
SOSO:0001244
PDB structuresPDBe

Expression and regulation

miR-122 was originally identified by cloning of tissue-specific microRNAs in mouse, where its expression is restricted to the liver.[2] The liver-specific expression of miR-122 is conserved in zebrafish.[3] miR-122 expression increases during embryogenesis until it constitutes 72% of total miRNA in adult human liver, making it one of the most highly expressed miRNAs in any tissue.[4] In humans, miR-122 is encoded at a single genomic locus in chromosome 18. The primary miR-122 transcript (pri-miR-122) is a long non-coding RNA. Transcription is regulated by HNF4α.[5] The miR-122 hairpin precursor consensus shown here is predicted based on base pairing and cross-species conservation. The mature sequence is excised from the 5′ arm of the hairpin.[2][6]

There is evidence that miR-122 is regulated by Rev-ErbA alpha which is involved in circadian gene expression, suggesting that miR-122 is a circadian metabolic regulator. miR-122 regulates the expression of several mRNA molecules that are important in the circadian cycle, such as PPARβ/δ.[7] Mature miR-122 is subject to modification by the poly(A) polymerase GLD-2, which adds a single adenosine to the miRNA 3′ end. This results in an increase in miR-122 stability.[8]

Targets

miR-122 regulates the synthesis of the protein CAT-1 by binding to sites in the mRNA 3'UTR such that translation is repressed and the mRNA is targeted to P bodies. This repression can be relieved by the protein HuR, which is released from the nucleus under conditions of cell stress and binds to the CAT-1 3'UTR. The HuR interaction leads to release of the mRNA from the P bodies and resumption of active translation.[9]

A number of other miR-122 targets, including CD320, AldoA and BCKDK, have been identified by microarray analysis of changes in mRNA expression in the liver of mice treated with miR-122 inhibitors.[10][11][12] The overall effect of miR-122 inhibition is to reduce the plasma cholesterol level, although the pathways involved in this regulation have not been fully elucidated. miR-122 also regulates systemic iron homeostasis via the target mRNAs Hjv and Hfe.[13] miR-122 inhibition in mice or primates does not result in any detectable liver toxicity.[14]

Role in cancer

miR-122 levels are frequently reduced in hepatocellular carcinoma (HCC) compared to normal liver, and low miR-122 levels correlate with poor prognosis.[15][16] Overexpression of miR-122 reduces tumorigenic properties in HCC cell lines, suggesting that it functions as a tumor suppressor gene, and increases the response of cells to the chemotherapeutic drugs sorafenib and doxorubicin.[17][18] Several miR-122 target genes have been implicated in tumorigenesis, including ADAM10, IGF1R, CCNG1 and ADAM17.[17][18][19]

Innate Immunity

Recent studies demonstrated that miR-122 may directly regulate different aspects of the interferons (IFNs) signaling pathway[20][21] to enhanced induction of anti-viral genes and inhibition of various virus.[21][22][23][24][25][26][27][28][29][30] Moreover, miR-122 have been shown to target various genes,[31][32][33][34][35] resulting in enhancement of IFN signaling and subsequent antiviral innate immunity.[31][36] Interferons (IFNs, includes type I and III interferon) treatment leads to a significant reduction in the expression of the liver-specific miR-122.[21][37][38][39][40] HepG2 cells with overexpressed microRNA-122 mount an effective antiviral interferon response and innate immune response to hepatitis C virus (HCV), other RNA viruses and viral mimetics (e.g. poly(I:C)).[22]

Regulation of HCV

Recent studies have shown that replication of hepatitis C virus (HCV) is dependent on miR-122 expression.[41] miR-122 regulates HCV by binding directly to two adjacent sites close to the 5′ end of HCV RNA.[42] Although these experiments were conducted using genotype 1a and 1b HCV RNA, the miR-122 binding sites are highly conserved across different genotypes, and miR-122 is also required for replication of infectious type 2a HCV.[43] As miRNAs generally function to repress gene expression by binding to 3'UTR sites, this positive regulation of viral replication via a 5'UTR represents a novel function for miR-122. The mechanism of regulation is not yet clear. miR-122 stimulates translation of HCV RNA, but not to a sufficient extent to explain its effects on viral replication, indicating that a second stage of the viral replication cycle must also be regulated. [44][45] HCV RNA synthesis is not affected by miR-122, suggesting that regulation of other processes such as RNA stability may occur.[46][47] The extent to which the miRNA-induced silencing complex (miRISC) is involved in this regulation has not been fully determined. The Argonaute proteins (Ago1–4), which are essential for miRNA-directed repression, appear to be necessary for miR-122 to regulate HCV,[48] although miR-122 overexpression may overcome this requirement.[49] Another miRISC component, the DEAD-box RNA helicase DDX6, does not play a role in miR-122-facilitated HCV replication.[50]

The existing HCV therapy of PEG-IFNα plus ribavirin is poorly tolerated and frequently ineffective,[51][52] so there is an urgent need for new drugs, and miR-122 inhibitors are an attractive possibility. The association between low miR-122 levels and hepatocellular carcinoma suggests that caution will be necessary when testing miR-122 inhibitors, and that long term treatment might be undesirable. However, miR-122 is a promising target as it can be very selectively and effectively inhibited with antisense oligonucleotides, and as it is a conserved host factor it is hoped that the virus would not be able to acquire resistance mutations to an anti-miR-122 therapeutic. Moreover, engineering HepG2 cells to express miR-122 (HepG2-HFL cell, HepG2 cells expressing miR-122) mount an effective antiviral interferon-lambda (IFNλ) based innate immune response to hepatitis C virus (HCV) infection.[22][53] HepG2 cells (stably expressing miR-122) produced a more robust IFN Response (type I and type III interferons) when challenged with other RNA viruses [ IAV-ΔNS1 and SeV ] and viral mimetics than Huh-7 and Huh-7.5 cells. HCV Induces an IFN-λ (IL28 and IL29), ISG, and Cytokine Response in these HepG2 cells with stably expressing miR-122.[22][23][54][31][55]

Inhibitor miravirsen

As of 2017, Santaris Pharma was developing miravirsen, a locked nucleic acid-based antisense oligonucleotide that inhibits miR-122, as a potential treatment for HepC.[56]

Use as a biomarker

miR-122 has recently been explored as a potential biomarker for various hepatic conditions. A change in levels of miR-122 in the blood has been confirmed as an indicator for viral-, alcohol- and chemical-induced liver injury [57][58][59] as well as Transplant rejection after Liver transplantation.[60][61] This change is noted before increased amino-transferase activity, making it an early indicator of liver disease and hepatocellular injury of liver grafts prior to liver transplantation.[62][63]

There is a great deal of research into the use of miR-122 as a biomarker for hepatitis C. While some studies dispute its efficacy for diagnosing Hep C,[64] other research indicates that it may be useful in diagnosing specific forms of hepatitis.[65] In addition, decreased levels of miR-122 in liver biopsies have been linked to a strain of hepatitis C that is resistant to interferon therapy.[66]

miR-122 has also been suggested as a biomarker for hepatectomy-induced liver injury in patients with hepatocellular carcinoma.[67]

It is important to note that detection of miR-122 and other microRNAs in Body fluid like blood can be interfered by heparin contaminated. The commonly used anticoagulant heparin profoundly inhibits the by reverse transcription polymerase chain reaction (RT-PCR) used for microRNA quantification.[68][69]

References
  1. "miRBase".
  2. Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T (2002). "Identification of tissue-specific microRNAs from mouse". Curr Biol. 12 (9): 735–739. doi:10.1016/S0960-9822(02)00809-6. PMID 12007417.
  3. Wienholds E, Kloosterman WP, Miska E, Alvarez-Saavedra E, Berezikov E, de Bruijn E, Horvitz HR, Kauppinen S, Plasterk RH (2005). "MicroRNA expression in zebrafish embryonic development". Science. 309 (5732): 310–311. doi:10.1126/science.1114519. PMID 15919954.
  4. Chang J, Nicolas E, Marks D, Sander C, Lerro A, Buendia MA, xu C, Mason WS, Moloshok T, Bort R, Zaret KS, Taylor JM (2004). "miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and mat downregulate the high affinity cationic amino acid transporter CAT-1". RNA Biology. 1 (2): 106–113. doi:10.4161/rna.1.2.1066. PMID 17179747.
  5. Li, Zhen-Ya; Xi, Yang, Zhu, Wen-Nan, Zeng, Chao, Zhang, Zhu-Qin, Guo, Zhi-Chen, Hao, De-Long, Liu, Guang, Feng, Lei, Chen, Hou-Zao, Chen, Feng, Lv, Xiang, Liu, De-Pei, Liang, Chih-Chuan (2011). "Positive regulation of hepatic miR-122 expression by HNF4α". Journal of Hepatology. 55 (3): 602–611. doi:10.1016/j.jhep.2010.12.023. PMID 21241755.CS1 maint: multiple names: authors list (link)
  6. Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V (2004). "Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation". Genome Biol. 5 (3): R13. doi:10.1186/gb-2004-5-3-r13. PMC 395763. PMID 15003116.
  7. Gatfield D, Le Martelot G, Vejnar CE, Gerlach D, Schaad O, Fleury-Olela F, Ruskeepää AL, Oresic M, Esau CC, Zdobnov EM, Schibler U (2009). "Integration of microRNA miR-122 in hepatic circadian gene expression". Genes Dev. 23 (11): 1313–1326. doi:10.1101/gad.1781009. PMC 2701584. PMID 19487572.
  8. Katoh, T.; Sakaguchi, Y., Miyauchi, K., Suzuki, T., Kashiwabara, S.-i., Baba, T., Suzuki, T. (2009). "Selective stabilization of mammalian microRNAs by 3′ adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2". Genes & Development. 23 (4): 433–438. doi:10.1101/gad.1761509. PMC 2648654. PMID 19240131.CS1 maint: multiple names: authors list (link)
  9. Bhattacharyya, Suvendra N.; Habermacher, Regula, Martine, Ursula, Closs, Ellen I., Filipowicz, Witold (June 2006). "Relief of microRNA-Mediated Translational Repression in Human Cells Subjected to Stress". Cell. 125 (6): 1111–1124. doi:10.1016/j.cell.2006.04.031. PMID 16777601.CS1 maint: multiple names: authors list (link)
  10. Krützfeldt, Jan; Rajewsky, Nikolaus, Braich, Ravi, Rajeev, Kallanthottathil G., Tuschl, Thomas, Manoharan, Muthiah, Stoffel, Markus (December 2005). "Silencing of microRNAs in vivo with 'antagomirs'". Nature. 438 (7068): 685–689. doi:10.1038/nature04303. PMID 16258535.CS1 maint: multiple names: authors list (link)
  11. Esau, Christine; Davis, Scott, Murray, Susan F., Yu, Xing Xian, Pandey, Sanjay K., Pear, Michael, Watts, Lynnetta, Booten, Sheri L., Graham, Mark, McKay, Robert, Subramaniam, Amuthakannan, Propp, Stephanie, Lollo, Bridget A., Freier, Susan, Bennett, C. Frank, Bhanot, Sanjay, Monia, Brett P. (2006). "miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting". Cell Metabolism. 3 (2): 87–98. doi:10.1016/j.cmet.2006.01.005. PMID 16459310.CS1 maint: multiple names: authors list (link)
  12. Elmén J, Lindow M, Silahtaroglu A, et al. (March 2008). "Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver". Nucleic Acids Res. 36 (4): 1153–1162. doi:10.1093/nar/gkm1113. PMC 2275095. PMID 18158304.
  13. Castoldi, Mirco; Vujic Spasic, Maja, Altamura, Sandro, Elmén, Joacim, Lindow, Morten, Kiss, Judit, Stolte, Jens, Sparla, Richard, D'Alessandro, Lorenza A., Klingmüller, Ursula, Fleming, Robert E., Longerich, Thomas, Gröne, Hermann J., Benes, Vladimir, Kauppinen, Sakari, Hentze, Matthias W., Muckenthaler, Martina U. (2011). "The liver-specific microRNA miR-122 controls systemic iron homeostasis in mice". Journal of Clinical Investigation. 121 (4): 1386–1396. doi:10.1172/JCI44883. PMC 3069782. PMID 21364282.CS1 maint: multiple names: authors list (link)
  14. Elmén, Joacim; Lindow, Morten, Schütz, Sylvia, Lawrence, Matthew, Petri, Andreas, Obad, Susanna, Lindholm, Marie, Hedtjärn, Maj, Hansen, Henrik Frydenlund, Berger, Urs, Gullans, Steven, Kearney, Phil, Sarnow, Peter, Straarup, Ellen Marie, Kauppinen, Sakari (April 2008). "LNA-mediated microRNA silencing in non-human primates". Nature. 452 (7189): 896–899. doi:10.1038/nature06783. PMID 18368051.CS1 maint: multiple names: authors list (link)
  15. Kutay, Huban; Bai, Shoumei, Datta, Jharna, Motiwala, Tasneem, Pogribny, Igor, Frankel, Wendy, Jacob, Samson T., Ghoshal, Kalpana (2006). "Downregulation of miR-122 in the rodent and human hepatocellular carcinomas". Journal of Cellular Biochemistry. 99 (3): 671–678. doi:10.1002/jcb.20982. PMC 3033198. PMID 16924677.CS1 maint: multiple names: authors list (link)
  16. Coulouarn, C; Factor, V M, Andersen, J B, Durkin, M E, Thorgeirsson, S S (October 2009). "Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties". Oncogene. 28 (40): 3526–3536. doi:10.1038/onc.2009.211. PMC 3492882. PMID 19617899.CS1 maint: multiple names: authors list (link)
  17. Bai, S.; Nasser, M. W., Wang, B., Hsu, S.-H., Datta, J., Kutay, H., Yadav, A., Nuovo, G., Kumar, P., Ghoshal, K. (2009). "MicroRNA-122 Inhibits Tumorigenic Properties of Hepatocellular Carcinoma Cells and Sensitizes These Cells to Sorafenib". Journal of Biological Chemistry. 284 (46): 32015–32027. doi:10.1074/jbc.M109.016774. PMC 2797273. PMID 19726678.CS1 maint: multiple names: authors list (link)
  18. Fornari, F.; Gramantieri, L., Giovannini, C., Veronese, A., Ferracin, M., Sabbioni, S., Calin, G. A., Grazi, G. L., Croce, C. M., Tavolari, S., Chieco, P., Negrini, M., Bolondi, L. (July 2009). "MiR-122/Cyclin G1 Interaction Modulates p53 Activity and Affects Doxorubicin Sensitivity of Human Hepatocarcinoma Cells". Cancer Research. 69 (14): 5761–5767. doi:10.1158/0008-5472.CAN-08-4797. PMID 19584283.CS1 maint: multiple names: authors list (link)
  19. Tsai, Wei-Chih; Hsu, Paul Wei-Che, Lai, Tsung-Ching, Chau, Gar-Yang, Lin, Ching-Wen, Chen, Chun-Ming, Lin, Chien-Der, Liao, Yu-Lun, Wang, Jui-Ling, Chau, Yat-Pang, Hsu, Ming-Ta, Hsiao, Michael, Huang, Hsien-Da, Tsou, Ann-Ping (May 2009). "MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma". Hepatology. 49 (5): 1571–1582. doi:10.1002/hep.22806. PMID 19296470.CS1 maint: multiple names: authors list (link)
  20. Wilson, JA; Sagan, SM (August 2014). "Hepatitis C virus and human miR-122: insights from the bench to the clinic". Current Opinion in Virology. 7: 11–18. doi:10.1016/j.coviro.2014.03.005. PMID 24721497.
  21. Forster, SC; Tate, MD; Hertzog, PJ (2015). "MicroRNA as Type I Interferon-Regulated Transcripts and Modulators of the Innate Immune Response". Frontiers in Immunology. 6: 334. doi:10.3389/fimmu.2015.00334. PMC 4495342. PMID 26217335.
  22. Israelow, B; Narbus, CM; Sourisseau, M; Evans, MJ (October 2014). "HepG2 cells mount an effective antiviral interferon-lambda based innate immune response to hepatitis C virus infection". Hepatology. 60 (4): 1170–1179. doi:10.1002/hep.27227. PMC 4176518. PMID 24833036.
  23. Park, H; Serti, E; Eke, O; Muchmore, B; Prokunina-Olsson, L; Capone, S; Folgori, A; Rehermann, B (December 2012). "IL-29 is the dominant type III interferon produced by hepatocytes during acute hepatitis C virus infection". Hepatology. 56 (6): 2060–2070. doi:10.1002/hep.25897. PMC 3581145. PMID 22706965.
  24. Thomas, E; Gonzalez, VD; Li, Q; Modi, AA; Chen, W; Noureddin, M; Rotman, Y; Liang, TJ (April 2012). "HCV infection induces a unique hepatic innate immune response associated with robust production of type III interferons". Gastroenterology. 142 (4): 978–988. doi:10.1053/j.gastro.2011.12.055. PMC 3435150. PMID 22248663.
  25. Narbus, CM; Israelow, B; Sourisseau, M; Michta, ML; Hopcraft, SE; Zeiner, GM; Evans, MJ (November 2011). "HepG2 cells expressing microRNA miR-122 support the entire hepatitis C virus life cycle". Journal of Virology. 85 (22): 12087–12092. doi:10.1128/jvi.05843-11. PMC 3209320. PMID 21917968.
  26. Sarasin-Filipowicz, M; Krol, J; Markiewicz, I; Heim, MH; Filipowicz, W (January 2009). "Decreased levels of microRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapy". Nature Medicine. 15 (1): 31–33. doi:10.1038/nm.1902. PMID 19122656.
  27. Li, A; Qian, J; He, J; Zhang, Q; Zhai, A; Song, W; Li, Y; Ling, H; Zhong, Z; Zhang, F (February 2013). "Modulation of miR‑122 expression affects the interferon response in human hepatoma cells". Molecular Medicine Reports. 7 (2): 585–590. doi:10.3892/mmr.2012.1233. PMID 23241652.
  28. Hao, J; Jin, W; Li, X; Wang, S; Zhang, X; Fan, H; Li, C; Chen, L; Gao, B; Liu, G; Meng, S (January 2013). "Inhibition of alpha interferon (IFN-α)-induced microRNA-122 negatively affects the anti-hepatitis B virus efficiency of IFN-α". Journal of Virology. 87 (1): 137–147. doi:10.1128/jvi.01710-12. PMC 3536426. PMID 23055569.
  29. Gao, D; Zhai, A; Qian, J; Li, A; Li, Y; Song, W; Zhao, H; Yu, X; Wu, J; Zhang, Q; Kao, W; Wei, L; Zhang, F; Zhong, Z (June 2015). "Down-regulation of suppressor of cytokine signaling 3 by miR-122 enhances interferon-mediated suppression of hepatitis B virus". Antiviral Research. 118: 20–28. doi:10.1016/j.antiviral.2015.03.001. PMID 25766860.
  30. He, J; Ji, Y; Li, A; Zhang, Q; Song, W; Li, Y; Huang, H; Qian, J; Zhai, A; Yu, X; Zhao, J; Shang, Q; Wei, L; Zhang, F (2014). "MiR-122 directly inhibits human papillomavirus E6 gene and enhances interferon signaling through blocking suppressor of cytokine signaling 1 in SiHa cells". PLOS ONE. 9 (9): e108410. doi:10.1371/journal.pone.0108410. PMC 4180754. PMID 25265013.
  31. Li, A; Song, W; Qian, J; Li, Y; He, J; Zhang, Q; Li, W; Zhai, A; Kao, W; Hu, Y; Li, H; Wu, J; Ling, H; Zhong, Z; Zhang, F (April 2013). "MiR-122 modulates type I interferon expression through blocking suppressor of cytokine signaling 1". The International Journal of Biochemistry & Cell Biology. 45 (4): 858–865. doi:10.1016/j.biocel.2013.01.008. PMID 23348614.
  32. Xiong, Y; Zhang, C; Yuan, J; Zhu, Y; Tan, Z; Kuang, X; Wang, X (March 2015). "Hepatitis C virus represses the cellular antiviral response by upregulating the expression of signal transducer and activator of transcription 3 through sponging microRNA‑122". Molecular Medicine Reports. 11 (3): 1733–1737. doi:10.3892/mmr.2014.2897. PMC 4270330. PMID 25377467.
  33. Gao, D; Zhai, A; Qian, J; Li, A; Li, Y; Song, W; Zhao, H; Yu, X; Wu, J; Zhang, Q; Kao, W; Wei, L; Zhang, F; Zhong, Z (June 2015). "Down-regulation of suppressor of cytokine signaling 3 by miR-122 enhances interferon-mediated suppression of hepatitis B virus". Antiviral Research. 118: 20–28. doi:10.1016/j.antiviral.2015.03.001. PMID 25766860.
  34. Yoshikawa, T; Takata, A; Otsuka, M; Kishikawa, T; Kojima, K; Yoshida, H; Koike, K (2012). "Silencing of microRNA-122 enhances interferon-α signaling in the liver through regulating SOCS3 promoter methylation". Scientific Reports. 2: 637. doi:10.1038/srep00637. PMC 3434395. PMID 22957141.
  35. Hao, J; Jin, W; Li, X; Wang, S; Zhang, X; Fan, H; Li, C; Chen, L; Gao, B; Liu, G; Meng, S (January 2013). "Inhibition of alpha interferon (IFN-α)-induced microRNA-122 negatively affects the anti-hepatitis B virus efficiency of IFN-α". Journal of Virology. 87 (1): 137–147. doi:10.1128/jvi.01710-12. PMC 3536426. PMID 23055569.
  36. Li, A; Qian, J; He, J; Zhang, Q; Zhai, A; Song, W; Li, Y; Ling, H; Zhong, Z; Zhang, F (February 2013). "Modulation of miR‑122 expression affects the interferon response in human hepatoma cells". Molecular Medicine Reports. 7 (2): 585–590. doi:10.3892/mmr.2012.1233. PMID 23241652.
  37. Pedersen, IM; Cheng, G; Wieland, S; Volinia, S; Croce, CM; Chisari, FV; David, M (18 October 2007). "Interferon modulation of cellular microRNAs as an antiviral mechanism". Nature. 449 (7164): 919–922. doi:10.1038/nature06205. PMC 2748825. PMID 17943132.
  38. Lee, HC; Narayanan, S; Park, SJ; Seong, SY; Hahn, YS (21 February 2014). "Transcriptional regulation of IFN-λ genes in hepatitis C virus-infected hepatocytes via IRF-3·IRF-7·NF-κB complex". The Journal of Biological Chemistry. 289 (8): 5310–5319. doi:10.1074/jbc.m113.536102. PMC 3931086. PMID 24385435.
  39. Aboulnasr, F; Hazari, S; Nayak, S; Chandra, PK; Panigrahi, R; Ferraris, P; Chava, S; Kurt, R; Song, K; Dash, A; Balart, LA; Garry, RF; Wu, T; Dash, S (2015). "IFN-λ Inhibits MiR-122 Transcription through a Stat3-HNF4α Inflammatory Feedback Loop in an IFN-α Resistant HCV Cell Culture System". PLOS ONE. 10 (12): e0141655. doi:10.1371/journal.pone.0141655. PMC 4686105. PMID 26657215.
  40. Hao, J; Jin, W; Li, X; Wang, S; Zhang, X; Fan, H; Li, C; Chen, L; Gao, B; Liu, G; Meng, S (January 2013). "Inhibition of alpha interferon (IFN-α)-induced microRNA-122 negatively affects the anti-hepatitis B virus efficiency of IFN-α". Journal of Virology. 87 (1): 137–147. doi:10.1128/jvi.01710-12. PMC 3536426. PMID 23055569.
  41. Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P (2005). "Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA". Science. 309 (5740): 1577–1581. doi:10.1126/science.1113329. PMID 16141076.
  42. Jopling, L.; Schütz, S.; Sarnow, P. (July 2008). "Position-dependent function for a tandem microRNA miR-122-binding site located in the hepatitis C virus RNA genome". Cell Host & Microbe. 4 (1): 77–85. doi:10.1016/j.chom.2008.05.013. ISSN 1931-3128. PMC 3519368. PMID 18621012.
  43. Randall G, Panis M, Cooper JD, Tellinghuisen TL, Sukhodolets KE, Pfeffer S, Landthaler M, Landgraf P, Kan S, Lindenbach BD, Chien M, Weir DB, Russo JJ, Ju J, Brownstein MJ, Sheridan R, Sander C, Zavolan M, Tuschl T, Rice CM (2007). "Cellular cofactors affecting hepatitis C virus infection and replication". Proc Natl Acad Sci U S A. 104 (31): 12884–12889. doi:10.1073/pnas.0704894104. PMC 1937561. PMID 17616579.
  44. Henke JI, Goergen D, Zheng J, Song Y, Schüttler CG, Fehr C, Jünemann C, Niepmann M (2008). "microRNA-122 stimulates translation of hepatitis C virus RNA". EMBO J. 27 (24): 3300–3310. doi:10.1038/emboj.2008.244. PMC 2586803. PMID 19020517.
  45. Jangra RK, Yi M, Lemon SM (2010). "Regulation of hepatitis C virus translation and infectious virus production by the microRNA miR-122". J Virol. 84 (13): 6615–6625. doi:10.1128/JVI.00417-10. PMC 2903297. PMID 20427538.
  46. Norman, K. L.; Sarnow, P. (2010). "Modulation of Hepatitis C Virus RNA Abundance and the Isoprenoid Biosynthesis Pathway by MicroRNA miR-122 Involves Distinct Mechanisms". Journal of Virology. 84 (1): 666–670. doi:10.1128/JVI.01156-09. PMC 2798415. PMID 19846523.
  47. Villanueva RA, Jangra RK, Yi M, Pyles R, Bourne N, Lemon SM (2010). "miR-122 does not modulate the elongation phase of hepatitis C virus RNA synthesis in isolated replicase complexes". Antiviral Res. 88 (1): 119–123. doi:10.1016/j.antiviral.2010.07.004. PMC 4422393. PMID 20637242.
  48. Wilson JA, Zhang C, Huys A, Richardson CD (2010). "Human Ago2 is required for efficient miR-122 regulation of HCV RNA accumulation and translation". J Virol. 85 (5): 2342–2350. doi:10.1128/JVI.02046-10. PMC 3067765. PMID 21177824.
  49. Machlin, E. S.; Sarnow, P., Sagan, S. M. (2011). "From the Cover: Masking the 5′ terminal nucleotides of the hepatitis C virus genome by an unconventional microRNA-target RNA complex". Proceedings of the National Academy of Sciences. 108 (8): 3193–3198. doi:10.1073/pnas.1012464108. PMC 3044371. PMID 21220300.CS1 maint: multiple names: authors list (link)
  50. Jangra RK, Yi M, Lemon SM (2010). "DDX6 (Rck/p54) is required for efficient hepatitis C virus replication but not for internal ribosome entry site-directed translation". J Virol. 84 (13): 6810–6824. doi:10.1128/JVI.00397-10. PMC 2903299. PMID 20392846.
  51. Urban, TJ; Thompson, AJ; Bradrick, SS; Fellay, J; Schuppan, D; Cronin, KD; Hong, L; McKenzie, A; Patel, K; Shianna, KV; McHutchison, JG; Goldstein, DB; Afdhal, N (December 2010). "IL28B genotype is associated with differential expression of intrahepatic interferon-stimulated genes in patients with chronic hepatitis C". Hepatology. 52 (6): 1888–1896. doi:10.1002/hep.23912. PMC 3653303. PMID 20931559.
  52. Sarasin-Filipowicz, M; Krol, J; Markiewicz, I; Heim, MH; Filipowicz, W (January 2009). "Decreased levels of microRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapy". Nature Medicine. 15 (1): 31–33. doi:10.1038/nm.1902. PMID 19122656.
  53. Narbus, CM; Israelow, B; Sourisseau, M; Michta, ML; Hopcraft, SE; Zeiner, GM; Evans, MJ (November 2011). "HepG2 cells expressing microRNA miR-122 support the entire hepatitis C virus life cycle". Journal of Virology. 85 (22): 12087–12092. doi:10.1128/jvi.05843-11. PMC 3209320. PMID 21917968.
  54. Thomas, E; Gonzalez, VD; Li, Q; Modi, AA; Chen, W; Noureddin, M; Rotman, Y; Liang, TJ (April 2012). "HCV infection induces a unique hepatic innate immune response associated with robust production of type III interferons". Gastroenterology. 142 (4): 978–988. doi:10.1053/j.gastro.2011.12.055. PMC 3435150. PMID 22248663.
  55. Li, A; Qian, J; He, J; Zhang, Q; Zhai, A; Song, W; Li, Y; Ling, H; Zhong, Z; Zhang, F (February 2013). "Modulation of miR‑122 expression affects the interferon response in human hepatoma cells". Molecular Medicine Reports. 7 (2): 585–590. doi:10.3892/mmr.2012.1233. PMID 23241652.
  56. Titze-de-Almeida, R; David, C; Titze-de-Almeida, SS (July 2017). "The Race of 10 Synthetic RNAi-Based Drugs to the Pharmaceutical Market". Pharmaceutical Research. 34 (7): 1339–1363. doi:10.1007/s11095-017-2134-2. PMID 28389707.
  57. Wang, Kai; Shile Zhang, Bruz Marzolf, Pamela Troisch, Amy Brightman, Zhiyuan Hu, Leroy E. Hood, and David J. Galas (17 March 2009). "Circulating microRNAs, potential biomarkers for drug-induced liver injury". PNAS. 106 (11): 4402–4407. doi:10.1073/pnas.0813371106. PMC 2657429. PMID 19246379.CS1 maint: multiple names: authors list (link)
  58. Bihrer, V; Friedrich-Rust M, Kronenberger B, Forestier N, Haupenthal J, Shi Y, Peveling-Oberhag J, Radeke HH, Sarrazin C, Herrmann E, Zeuzem S, Waidmann O, Piiper A. (24 May 2011). "Serum miR-122 as a biomarker of necroinflammation in patients with chronic hepatitis C virus infection". American Journal of Gastroenterology. 106 (9): 1663–1669. doi:10.1038/ajg.2011.161. hdl:10033/214238. PMID 21606975.CS1 maint: multiple names: authors list (link)
  59. Dirksen, K; Verzijl, T; Van Den Ingh, T.S.G.A.M; Vernooij, J.C.M; Van Der Laan, L.J.W; Burgener, I.A; Spee, B; Fieten, H (2016). "Hepatocyte-derived microRNAs as sensitive serum biomarkers of hepatocellular injury in Labrador retrievers". The Veterinary Journal. 211: 75–81. doi:10.1016/j.tvjl.2016.01.010. PMID 27021912.
  60. Farid, Waqar R. R; Pan, Qiuwei; Van Der Meer, Adriaan J. P; De Ruiter, Petra E; Ramakrishnaiah, Vedashree; De Jonge, Jeroen; Kwekkeboom, Jaap; Janssen, Harry L. A; Metselaar, Herold J; Tilanus, Hugo W; Kazemier, Geert; Van Der Laan, Luc J.W (2012). "Hepatocyte-derived microRNAs as serum biomarkers of hepatic injury and rejection after liver transplantation". Liver Transplantation. 18 (3): 290–297. doi:10.1002/lt.22438. PMID 21932376.
  61. Verhoeven, CJ, van der Laan, LJ, de Jonge, J, Metselaar, HJ (2017). Biomarkers to Monitor Graft Function Following Liver Transplantation. Biomarkers in Liver Disease. V. B. Patel and V. R. Preedy. Dordrecht, Springer Netherlands: ISBN 978-94-007-7675-3, page 193–220.
  62. Farid, Waqar R. R; Pan, Qiuwei; Van Der Meer, Adriaan J. P; De Ruiter, Petra E; Ramakrishnaiah, Vedashree; De Jonge, Jeroen; Kwekkeboom, Jaap; Janssen, Harry L. A; Metselaar, Herold J; Tilanus, Hugo W; Kazemier, Geert; Van Der Laan, Luc J.W (2012). "Hepatocyte-derived microRNAs as serum biomarkers of hepatic injury and rejection after liver transplantation". Liver Transplantation. 18 (3): 290–297. doi:10.1002/lt.22438. PMID 21932376.
  63. Selten, Jasmijn W; Verhoeven, Cornelia J; Heedfeld, Veerle; Roest, Henk P; De Jonge, Jeroen; Pirenne, Jacques; Van Pelt, Jos; Ijzermans, Jan. N. M; Monbaliu, Diethard; Van Der Laan, Luc J. W (2017). "The release of microRNA-122 during liver preservation is associated with early allograft dysfunction and graft survival after transplantation". Liver Transplantation. 23 (7): 946–956. doi:10.1002/lt.24766. PMID 28388830.
  64. Morita, Kazutoyo; Taketomi, Akinobu; Shirabe, Ken; Umeda, Kenji; Kayashima, Hiroto; Ninomiya, Mizuki; Uchiyama, Hideaki; Soejima, Yuji; Maehara, Yoshihiko (April 2011). "Clinical significance and potential of hepatic microRNA-122 expression in hepatitis C". Liver International. 31 (4): 474–484. doi:10.1111/j.1478-3231.2010.02433.x. PMID 21199296.
  65. Van Der Meer, A. J; Farid, W. R. R; Sonneveld, M. J; De Ruiter, P. E; Boonstra, A; Van Vuuren, A. J; Verheij, J; Hansen, B. E; De Knegt, R. J; Van Der Laan, L. J. W; Janssen, H. L. A (2013). "Sensitive detection of hepatocellular injury in chronic hepatitis C patients with circulating hepatocyte-derived microRNA-122". Journal of Viral Hepatitis. 20 (3): 158–166. doi:10.1111/jvh.12001. PMID 23383654.
  66. Sarasin-Filipowicz, Magdalena; Jacek Krol, Ilona Markiewicz, Markus H Heim, Witold Filipowicz (4 January 2009). "Decreased levels of microRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapy". Nature Medicine. 15 (1): 31–33. doi:10.1038/nm.1902. PMID 19122656.CS1 maint: multiple names: authors list (link)
  67. Ruoquan Y (February 2014). "Correlation between plasma miR-122 expression and liver injury induced by hepatectomy". J Int Med Res. 42 (1): 77–84. doi:10.1177/0300060513499093. PMID 24287929.
  68. Roest, Henk P; Verhoeven, Cornelia J; De Haan, Jubi E; De Jonge, Jeroen; Ijzermans, Jan N.M; Van Der Laan, Luc J.W (2016). "Improving Accuracy of Urinary miRNA Quantification in Heparinized Patients Using Heparinase I Digestion". The Journal of Molecular Diagnostics. 18 (6): 825–833. doi:10.1016/j.jmoldx.2016.06.006. PMID 27598820.
  69. Verhoeven, Cornelia J; Selten, Jasmijn W; Roest, Henk P; Farid, Waqar R.R; De Ruiter, Petra E; Hansen, Bettina E; De Jonge, Jeroen; Kwekkeboom, Jaap; Metselaar, Herold J; Tilanus, Hugo W; Kazemier, Geert; Ijzermans, Jan N.M; Van Der Laan, Luc J.W (2017). "Addendum to "MicroRNA profiles in graft preservation solution are predictive of ischemic-type biliary lesions after liver transplantation" [J Hepatol 2013;59:1231–1238]". Journal of Hepatology. 67 (6): 1358. doi:10.1016/j.jhep.2017.09.001. PMID 28964525.

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