miR-122

mir-122 microRNA precursor
Predicted secondary structure and sequence conservation of mir-122
Identifiers
Symbol mir-122
Rfam RF00684
miRBase MI0000442
miRBase family MIPF0000095
Other data
RNA type Gene; miRNA
Domain(s) Eukaryota
GO 0035195 0035068
SO 0001244

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.

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]

miR-122 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 antiviral immune response

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. Interestingly, interferons (IFNs, includes type I and III interferon) treatment leads to a significant reduction in the expression of the liver-specific miR-122.[21][36][37][38][39]

Regulation of HCV

Recent studies have shown that replication of hepatitis C virus (HCV) is dependent on miR-122 expression.[40] miR-122 regulates HCV by binding directly to two adjacent sites close to the 5' end of HCV RNA.[41] 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.[42] 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.[43][44] HCV RNA synthesis is not affected by miR-122, suggesting that regulation of other processes such as RNA stability may occur.[45][46] 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,[47] although miR-122 overexpression may overcome this requirement.[48] Another miRISC component, the DEAD-box RNA helicase DDX6, does not play a role in miR-122-facilitated HCV replication.[49]

The existing HCV therapy of PEG-IFNα plus ribavirin is poorly tolerated and frequently ineffective,[50][51] 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][52] 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][53]

Inhibitor miravirsen

Main article: Miravirsen

Santaris Pharma are developing miravirsen, a locked nucleic acid-based antisense oligonucleotide that is delivered to the liver and effectively inhibits miR-122.[54] This molecule reduced HCV viremia in a small-scale trial in chimpanzees[55] and was found to be safe in a small trial in humans.[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 liver disease.[57][58] This change is noted before increased amino-transferase activity, making it a preferable indicator for liver disease. This study also suggested that miR-122 could be a "novel, predictive and reliable blood marker for viral-, alcohol- and chemical-induced liver injury."[5]

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,[59] other research indicates that it may be useful in diagnosing specific forms of hepatitis. For instance, decreased levels of miR-122 have been linked to a strain of hepatitis C that is resistant to interferon therapy.[60] In this case, measuring miR-122 levels in the bloodstream of hepatitis C positive patients would enable more accurate and personalized therapy for their disease.

miR-122 has also been suggested as a biomarker for hepatectomy-induced liver injury in patients with hepatocellular carcinoma.[61]

Further reading

  1. ↑ "miRBase".
  2. 1 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): 735–9. 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 RHA (2005). "MicroRNA expression in zebrafish embryonic development". Science 309 (5732): 310–1. 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. 1 2 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.
  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): 1313–26. 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. "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.
  9. ↑ Bhattacharyya, Suvendra N.; Habermacher, Regula, Martine, Ursula, Closs, Ellen I., Filipowicz, Witold. "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.
  10. ↑ Krützfeldt, Jan; Rajewsky, Nikolaus, Braich, Ravi, Rajeev, Kallanthottathil G., Tuschl, Thomas, Manoharan, Muthiah, Stoffel, Markus. "Silencing of microRNAs in vivo with ‘antagomirs’". Nature 438 (7068): 685–689. doi:10.1038/nature04303. PMID 16258535.
  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. "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.
  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): 1153–62. 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. "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.
  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. "LNA-mediated microRNA silencing in non-human primates". Nature 452 (7189): 896–899. doi:10.1038/nature06783. PMID 18368051.
  15. ↑ Kutay, Huban; Bai, Shoumei, Datta, Jharna, Motiwala, Tasneem, Pogribny, Igor, Frankel, Wendy, Jacob, Samson T., Ghoshal, Kalpana. "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.
  16. ↑ Coulouarn, C; Factor, V M, Andersen, J B, Durkin, M E, Thorgeirsson, S S. "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. PMID 19617899.
  17. 1 2 Bai, S.; Nasser, M. W., Wang, B., Hsu, S.-H., Datta, J., Kutay, H., Yadav, A., Nuovo, G., Kumar, P., Ghoshal, K. "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.
  18. 1 2 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. "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.
  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. "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.
  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: 11–8. PMID 24721497.
  21. 1 2 3 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. PMID 26217335.
  22. 1 2 3 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 (Baltimore, Md.) 60 (4): 1170–9. PMID 24833036.
  23. 1 2 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 (Baltimore, Md.) 56 (6): 2060–70. 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): 978–88. 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): 12087–92. 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): 31–3. 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): 585–90. 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): 137–47. 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: 20–8. 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. PMID 25265013.
  31. ↑ 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): 137–47. PMID 23055569.
  32. ↑ 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): 858–65. PMID 23348614.
  33. ↑ 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): 1733–7. PMID 25377467.
  34. ↑ 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: 20–8. PMID 25766860.
  35. ↑ 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. PMID 22957141.
  36. ↑ 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): 919–22. PMID 17943132.
  37. ↑ 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): 5310–9. PMID 24385435.
  38. ↑ 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. PMID 26657215.
  39. ↑ 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): 137–47. PMID 23055569.
  40. ↑ 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): 1577–81. doi:10.1126/science.1113329. PMID 16141076.
  41. ↑ Jopling, L.; Schütz, S.; Sarnow, P. (Jul 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.
  42. ↑ 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): 12884–9. doi:10.1073/pnas.0704894104. PMC 1937561. PMID 17616579.
  43. 1 2 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): 3300–10. doi:10.1038/emboj.2008.244. PMC 2586803. PMID 19020517.
  44. 1 2 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): 6615–25. doi:10.1128/JVI.00417-10. PMC 2903297. PMID 20427538.
  45. ↑ Norman, K. L.; Sarnow, P. "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.
  46. 1 2 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): 119–23. doi:10.1016/j.antiviral.2010.07.004. PMID 20637242.
  47. ↑ 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): 2342–50. doi:10.1128/JVI.02046-10. PMID 21177824.
  48. ↑ Machlin, E. S.; Sarnow, P., Sagan, S. M. "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.
  49. ↑ 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): 6810–24. doi:10.1128/JVI.00397-10. PMC 2903299. PMID 20392846.
  50. ↑ 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 (Baltimore, Md.) 52 (6): 1888–96. PMID 20931559.
  51. ↑ 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): 31–3. PMID 19122656.
  52. ↑ 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): 12087–92. PMID 21917968.
  53. ↑ 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): 978–88. PMID 22248663.
  54. ↑ Elmén J, Lindow M, Schütz S, Lawrence M, Petri A, Obad S, Lindholm M, Hedtjärn M, Hansen HF, Berger U, Gullans S, Kearney P, Sarnow P, Straarup EM, Kauppinen S (2008). "LNA-mediated microRNA silencing in non-human primates.". Nature 452 (7189): 896–9. doi:10.1038/nature06783. PMID 18368051.
  55. ↑ Lanford, R. E.; Hildebrandt-Eriksen, E. S., Petri, A., Persson, R., Lindow, M., Munk, M. E., Kauppinen, S., Orum, H. "Therapeutic Silencing of MicroRNA-122 in Primates with Chronic Hepatitis C Virus Infection". Science 327 (5962): 198–201. doi:10.1126/science.1178178. PMID 19965718.
  56. ↑ . doi:10.1016/j.antiviral.2014.08.015. Missing or empty |title= (help)
  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.
  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): 1663–9. doi:10.1038/ajg.2011.161. PMID 21606975.
  59. ↑ 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.
  60. ↑ 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.
  61. ↑ Ruoquan Y (Feb 2014). "Correlation between plasma miR-122 expression and liver injury induced by hepatectomy." (PDF). J Int Med Res 42 (1): 77–84. doi:10.1177/0300060513499093. PMID 24287929.
  62. ↑ Zeng C, Wang R, Li D, Lin XJ, Wei QK, Yuan Y, Wang Q, Chen W, Zhuang SM (2010). "A novel GSK-3 beta-C/EBP alpha-miR-122-insulin-like growth factor 1 receptor regulatory circuitry in human hepatocellular carcinoma.". Hepatology 52 (5): 1702–12. doi:10.1002/hep.23875. PMID 21038412.
  63. ↑ Shea CM, Tzertzinis G (2010). "Controlled expression of functional miR-122 with a ligand inducible expression system.". BMC Biotechnol 10 (1): 76. doi:10.1186/1472-6750-10-76. PMC 2976731. PMID 20961424.
  64. ↑ Stilling G, Sun Z, Zhang S, Jin L, Righi A, Kovācs G, Korbonits M, Scheithauer BW, Kovacs K, Lloyd RV (2010). "MicroRNA expression in ACTH-producing pituitary tumors: up-regulation of microRNA-122 and -493 in pituitary carcinomas.". Endocrine 38 (1): 67–75. doi:10.1007/s12020-010-9346-0. PMID 20960104.
  65. ↑ Zhang Y, Jia Y, Zheng R, Guo Y, Wang Y, Guo H, Fei M, Sun S (2010). "Plasma MicroRNA-122 as a Biomarker for Viral-, Alcohol-, and Chemical-Related Hepatic Diseases.". Clin Chem 56 (12): 1830–8. doi:10.1373/clinchem.2010.147850. PMID 20930130.
  66. ↑ Xu H, He JH, Xiao ZD, Zhang QQ, Chen YQ, Zhou H, Qu LH (2010). "Liver-enriched transcription factors regulate microRNA-122 that targets CUTL1 during liver development.". Hepatology 52 (4): 1431–42. doi:10.1002/hep.23818. PMID 20842632.
  67. ↑ Burchard J, Zhang C, Liu AM, Poon RT, Lee NP, Wong KF, Sham PC, Lam BY, Ferguson MD, Tokiwa G, Smith R, Leeson B, Beard R, Lamb JR, Lim L, Mao M, Dai H, Luk JM (2010). "microRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma.". Mol Syst Biol 6 (1): 402. doi:10.1038/msb.2010.58. PMC 2950084. PMID 20739924.
  68. ↑ Qiu L, Fan H, Jin W, Zhao B, Wang Y, Ju Y, Chen L, Chen Y, Duan Z, Meng S (2010). "miR-122-induced down-regulation of HO-1 negatively affects miR-122-mediated suppression of HBV.". Biochem Biophys Res Commun 398 (4): 771–7. doi:10.1016/j.bbrc.2010.07.021. PMID 20633528.
  69. ↑ Lin LT, Noyce RS, Pham TN, Wilson JA, Sisson GR, Michalak TI, Mossman KL, Richardson CD (2010). "Replication of subgenomic hepatitis C virus replicons in mouse fibroblasts is facilitated by deletion of interferon regulatory factor 3 and expression of liver-specific microRNA 122.". J Virol 84 (18): 9170–80. doi:10.1128/JVI.00559-10. PMC 2937658. PMID 20592082.
  70. ↑ Kojima S, Gatfield D, Esau CC, Green CB (2010). Yamazaki, Shin, ed. "MicroRNA-122 modulates the rhythmic expression profile of the circadian deadenylase Nocturnin in mouse liver.". PLoS ONE 5 (6): e11264. doi:10.1371/journal.pone.0011264. PMC 2889834. PMID 20582318.
  71. ↑ Qian J, Zhai A, Kao W, Li Y, Song W, Fu Y, Chen X, Zhang Q, Wu J, Li H, Zhong Z, Ling H, Zhang F (2010). "Modulation of miR-122 on persistently Borna disease virus infected human oligodendroglial cells.". Antiviral Res 87 (2): 249–56. doi:10.1016/j.antiviral.2010.05.011. PMID 20561966.
  72. ↑ Young DD, Connelly CM, Grohmann C, Deiters A (2010). "Small molecule modifiers of microRNA miR-122 function for the treatment of hepatitis C virus infection and hepatocellular carcinoma.". J Am Chem Soc 132 (23): 7976–81. doi:10.1021/ja910275u. PMID 20527935.
  73. ↑ Chang Y, He XX, Li PY, Lin JS (2010). "[MiR-122 regulates the expression of PEG10 in hepatoma cell lines]". Zhonghua Gan Zang Bing Za Zhi 18 (4): 288–91. doi:10.3760/cma.j.issn.1007-3418.2010.04.013. PMID 20460050.
  74. ↑ Lee TC, Lin YL, Liao JT, Su CM, Lin CC, Lin WP, Liao CL (2010). "Utilizing liver-specific microRNA-122 to modulate replication of dengue virus replicon.". Biochem Biophys Res Commun 396 (3): 596–601. doi:10.1016/j.bbrc.2010.04.080. PMID 20412785.
  75. ↑ Pfeffer S, Baumert TF (2010). Kowdley, Kris; McCaughan, Geoffrey; Trautwein, Christian, eds. "Antagonizing microRNA-122 and treatment of hepatitis C virus infection.". Hepatology 51 (4): 1461–3. doi:10.1002/hep.23573. PMID 20373371.
  76. ↑ Branch AD, Rice CM (2010). "Antisense gets a grip on miR-122 in chimpanzees.". Sci Transl Med 2 (13): 13ps1. doi:10.1126/scitranslmed.3000605. PMID 20371461.
  77. ↑ Norman KL, Sarnow P (2010). "Hepatitis C virus' Achilles' heel--dependence on liver-specific microRNA miR-122.". Cell Res 20 (3): 247–9. doi:10.1038/cr.2010.28. PMID 20190773.
  78. ↑ Ma L, Liu J, Shen J, Liu L, Wu J, Li W, Luo J, Chen Q, Qian C (2010). "Expression of miR-122 mediated by adenoviral vector induces apoptosis and cell cycle arrest of cancer cells.". Cancer Biol Ther 9 (7): 554–61. doi:10.4161/cbt.9.7.11267. PMID 20150764.
  79. ↑ Haussecker D, Kay MA (2010). "miR-122 continues to blaze the trail for microRNA therapeutics.". Mol Ther 18 (2): 240–2. doi:10.1038/mt.2009.313. PMC 2839286. PMID 20125164.
  80. ↑ Iliopoulos D, Drosatos K, Hiyama Y, Goldberg IJ, Zannis VI (2010). "MicroRNA-370 controls the expression of microRNA-122 and Cpt1alpha and affects lipid metabolism.". J Lipid Res 51 (6): 1513–23. doi:10.1194/jlr.M004812. PMC 3035515. PMID 20124555.
  81. ↑ Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, Munk ME, Kauppinen S, Ørum H (2010). "Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection.". Science 327 (5962): 198–201. doi:10.1126/science.1178178. PMID 19965718.
  82. ↑ Wu X, Wu S, Tong L, Luan T, Lin L, Lu S, Zhao W, Ma Q, Liu H, Zhong Z (2009). "miR-122 affects the viability and apoptosis of hepatocellular carcinoma cells.". Scand J Gastroenterol 44 (11): 1332–9. doi:10.3109/00365520903215305. PMID 19891584.
  83. ↑ Norman KL, Sarnow P (2010). "Modulation of hepatitis C virus RNA abundance and the isoprenoid biosynthesis pathway by microRNA miR-122 involves distinct mechanisms.". J Virol 84 (1): 666–70. doi:10.1128/JVI.01156-09. PMC 2798415. PMID 19846523.
  84. ↑ Bai S, Nasser MW, Wang B, Hsu SH, 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.". J Biol Chem 284 (46): 32015–27. doi:10.1074/jbc.M109.016774. PMC 2797273. PMID 19726678.
  85. ↑ Huang Z, Liu C (2009). "Construction and identification of the human liver-specific miR-122 expression vector". Sheng Wu Gong Cheng Xue Bao 25 (4): 587–90. PMID 19637636.
  86. ↑ Coulouarn C, Factor VM, Andersen JB, Durkin ME, Thorgeirsson SS (2009). "Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties.". Oncogene 28 (40): 3526–36. doi:10.1038/onc.2009.211. PMID 19617899.
  87. ↑ Zhang R, Wang L, Yu GR, Zhang X, Yao LB, Yang AG (2009). "MicroRNA-122 might be a double-edged sword in hepatocellular carcinoma.". Hepatology 50 (4): 1322–3. doi:10.1002/hep.23108. PMID 19591123.
  88. ↑ Fornari F, Gramantieri L, Giovannini C, Veronese A, Ferracin M, Sabbioni S, Calin GA, Grazi GL, Croce CM, Tavolari S, Chieco P, Negrini M, Bolondi L (2009). "MiR-122/cyclin G1 interaction modulates p53 activity and affects doxorubicin sensitivity of human hepatocarcinoma cells.". Cancer Res 69 (14): 5761–7. doi:10.1158/0008-5472.CAN-08-4797. PMID 19584283.
  89. ↑ Díaz-Toledano R, Ariza-Mateos A, Birk A, Martínez-García B, Gómez J (2009). "In vitro characterization of a miR-122-sensitive double-helical switch element in the 5' region of hepatitis C virus RNA.". Nucleic Acids Res 37 (16): 5498–510. doi:10.1093/nar/gkp553. PMC 2760801. PMID 19578061.
  90. ↑ Tsai WC, Hsu PW, Lai TC, Chau GY, Lin CW, Chen CM, Lin CD, Liao YL, Wang JL, Chau YP, Hsu MT, Hsiao M, Huang HD, Tsou AP (2009). "MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma.". Hepatology 49 (5): 1571–82. doi:10.1002/hep.22806. PMID 19296470.
  91. ↑ Sarasin-Filipowicz M, Krol J, Markiewicz I, Heim MH, Filipowicz W (2009). "Decreased levels of microRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapy.". Nat Med 15 (1): 31–3. doi:10.1038/nm.1902. PMID 19122656.
  92. ↑ Jopling CL (2008). "Regulation of hepatitis C virus by microRNA-122.". Biochem Soc Trans 36 (Pt 6): 1220–3. doi:10.1042/BST0361220. PMID 19021529.
  93. ↑ Lin CJ, Gong HY, Tseng HC, Wang WL, Wu JL (2008). "miR-122 targets an anti-apoptotic gene, Bcl-w, in human hepatocellular carcinoma cell lines.". Biochem Biophys Res Commun 375 (3): 315–20. doi:10.1016/j.bbrc.2008.07.154. PMID 18692484.
  94. ↑ Chang J, Guo JT, Jiang D, Guo H, Taylor JM, Block TM (2008). "Liver-specific microRNA miR-122 enhances the replication of hepatitis C virus in nonhepatic cells.". J Virol 82 (16): 8215–23. doi:10.1128/JVI.02575-07. PMC 2519557. PMID 18550664.
  95. ↑ Girard M, Jacquemin E, Munnich A, Lyonnet S, Henrion-Caude A (2008). "miR-122, a paradigm for the role of microRNAs in the liver.". J Hepatol 48 (4): 648–56. doi:10.1016/j.jhep.2008.01.019. PMID 18291553.
  96. ↑ Fabani MM, Gait MJ (2008). "miR-122 targeting with LNA/2'-O-methyl oligonucleotide mixmers, peptide nucleic acids (PNA), and PNA-peptide conjugates.". RNA 14 (2): 336–46. doi:10.1261/rna.844108. PMC 2212241. PMID 18073344.
  97. ↑ Jopling CL, Norman KL, Sarnow P (2006). "Positive and negative modulation of viral and cellular mRNAs by liver-specific microRNA miR-122.". Cold Spring Harb Symp Quant Biol 71: 369–76. doi:10.1101/sqb.2006.71.022. PMID 17381319.
  98. ↑ Kutay H, Bai S, Datta J, Motiwala T, Pogribny I, Frankel W, Jacob ST, Ghoshal K (2006). "Downregulation of miR-122 in the rodent and human hepatocellular carcinomas.". J Cell Biochem 99 (3): 671–8. doi:10.1002/jcb.20982. PMC 3033198. PMID 16924677.
  99. ↑ Conrad, KD; Giering, F; Erfurth, C; Neumann, A; Fehr, C; Meister, G; Niepmann, M (2013). "microRNA-122 Dependent Binding of Ago2 Protein to Hepatitis C Virus RNA Is Associated with Enhanced RNA Stability and Translation Stimulation.". PLoS ONE 8 (2): e56272. doi:10.1371/journal.pone.0056272. PMID 23405269.
  100. ↑ Mortimer, S. A.; Doudna, J. A. (2013). "Unconventional miR-122 binding stabilizes the HCV genome by forming a trimolecular RNA structure". Nucleic Acids Research 41 (7): 4230–40. doi:10.1093/nar/gkt075. PMID 23416544.

External links

miRNA precursor families
1-100
101-200
201+
Other
This article is issued from Wikipedia - version of the Monday, April 04, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.