{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T14:07:43Z","timestamp":1770818863726,"version":"3.50.1"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,3,16]],"date-time":"2016-03-16T00:00:00Z","timestamp":1458086400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,3,16]],"date-time":"2016-03-16T00:00:00Z","timestamp":1458086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The interplay between viral and host factors plays a major role in viral pathogenesis. Hepatitis B virus (HBV) infection is a global health problem that leads to liver cirrhosis and hepatocellular carcinoma (HCC). Although HBV proteins have been studied extensively about their implication in hepatocarcinogenesis, the molecular mechanisms of oncogenesis are still largely unknown. A recent concept in gene regulation, in which competitive endogenous RNAs compete for common microRNAs (miRNAs), suggests that mRNA targets are key elements in the regulation of miRNA availability. Here, we show that HBV mRNA in the preS2 region can be targeted by host miRNA let-7\u2009g. This leads to the sequestration of let-7\u2009g and inhibition of let-7\u2009g function. The expression of HBV transcripts, including the preS2 region, de-repressed let-7\u2009g targets, which may contribute to long-term oncogenesis. HBV transcript-expressing transgenic mice, but not non-targeted transcript-expressing mice, were more prone to chemically induced hepatoocarcinogenesis. Let-7 target protein expression was upregulated in human HCC tissues derived from HBV-infected patients. On the other hand, let-7\u2009g inhibited HBV preS2 protein expression and viral products. These results suggest that the interplay between viral intermediate transcripts during HBV replication and host miRNAs is crucial to the pathogenesis of chronic viral infection.<\/jats:p>","DOI":"10.1038\/srep23237","type":"journal-article","created":{"date-parts":[[2016,3,16]],"date-time":"2016-03-16T10:22:44Z","timestamp":1458123764000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Mutual antagonism between hepatitis B viral mRNA and host microRNA let-7"],"prefix":"10.1038","volume":"6","author":[{"given":"Akemi","family":"Takata","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motoyuki","family":"Otsuka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motoko","family":"Ohno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Kishikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Yoshikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiko","family":"Koike","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,3,16]]},"reference":[{"key":"BFsrep23237_CR1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.cell.2004.12.035","volume":"120","author":"BP Lewis","year":"2005","unstructured":"Lewis, B. P., Burge, C. B. & Bartel, D. P. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15\u201320, 10.1016\/j.cell.2004.12.035 (2005).","journal-title":"Cell"},{"key":"BFsrep23237_CR2","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","volume":"116","author":"DP Bartel","year":"2004","unstructured":"Bartel, D. P. MicroRNAs: genomics, biogenesis, mechanism and function. Cell 116, 281\u2013297 (2004).","journal-title":"Cell"},{"key":"BFsrep23237_CR3","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1038\/nature02871","volume":"431","author":"V Ambros","year":"2004","unstructured":"Ambros, V. The functions of animal microRNAs. Nature 431, 350\u2013355 (2004).","journal-title":"Nature"},{"key":"BFsrep23237_CR4","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/nature03702","volume":"435","author":"J Lu","year":"2005","unstructured":"Lu J. et al. MicroRNA expression profiles classify human cancers. Nature 435, 834\u2013838 (2005).","journal-title":"Nature"},{"key":"BFsrep23237_CR5","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1038\/nature09144","volume":"465","author":"L Poliseno","year":"2010","unstructured":"Poliseno, L. et al. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465, 1033\u20131038, 10.1038\/nature09144 (2010).","journal-title":"Nature"},{"key":"BFsrep23237_CR6","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1038\/nature12986","volume":"505","author":"Y Tay","year":"2014","unstructured":"Tay, Y., Rinn, J. & Pandolfi, P. P. The multilayered complexity of ceRNA crosstalk and competition. Nature 505, 344\u2013352, 10.1038\/nature12986 (2014).","journal-title":"Nature"},{"key":"BFsrep23237_CR7","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1097\/MCG.0b013e3182872f29","volume":"47","author":"S Mittal","year":"2013","unstructured":"Mittal, S. & El-Serag, H. B. Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol 47 Suppl, S2\u20136, 10.1097\/MCG.0b013e3182872f29 (2013).","journal-title":"J Clin Gastroenterol"},{"key":"BFsrep23237_CR8","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1126\/science.8211155","volume":"262","author":"DS Chen","year":"1993","unstructured":"Chen, D. S. From hepatitis to hepatoma: lessons from type B viral hepatitis. Science 262, 369\u2013370 (1993).","journal-title":"Science"},{"key":"BFsrep23237_CR9","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1159\/000080872","volume":"47","author":"H Norder","year":"2004","unstructured":"Norder, H. et al. Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes and HBsAg subtypes. Intervirology 47, 289\u2013309, 10.1159\/000080872 (2004).","journal-title":"Intervirology"},{"key":"BFsrep23237_CR10","doi-asserted-by":"publisher","first-page":"10538","DOI":"10.1128\/JVI.00462-09","volume":"83","author":"K Tatematsu","year":"2009","unstructured":"Tatematsu, K. et al. A genetic variant of hepatitis B virus divergent from known human and ape genotypes isolated from a Japanese patient and provisionally assigned to new genotype J. J Virol 83, 10538\u201310547, 10.1128\/JVI.00462-09 (2009).","journal-title":"J. J Virol"},{"key":"BFsrep23237_CR11","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1111\/j.1440-1746.2010.06545.x","volume":"26","author":"MF Yuen","year":"2011","unstructured":"Yuen, M. F. & Lai, C. L. Treatment of chronic hepatitis B: Evolution over two decades. J Gastroenterol Hepatol 26 Suppl 1, 138\u2013143, 10.1111\/j.1440-1746.2010.06545.x (2011).","journal-title":"J Gastroenterol Hepatol"},{"key":"BFsrep23237_CR12","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/0092-8674(86)90602-1","volume":"47","author":"JS Tuttleman","year":"1986","unstructured":"Tuttleman, J. S., Pourcel, C. & Summers, J. Formation of the pool of covalently closed circular viral DNA in hepadnavirus-infected cells. Cell 47, 451\u2013460 (1986).","journal-title":"Cell"},{"key":"BFsrep23237_CR13","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.chom.2008.05.002","volume":"3","author":"E Gottwein","year":"2008","unstructured":"Gottwein, E. & Cullen, B. R. Viral and cellular microRNAs as determinants of viral pathogenesis and immunity. Cell Host Microbe 3, 375\u2013387, 10.1016\/j.chom.2008.05.002 (2008).","journal-title":"Cell Host Microbe"},{"key":"BFsrep23237_CR14","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1101\/sqb.2006.71.022","volume":"71","author":"CL Jopling","year":"2006","unstructured":"Jopling, C. L., Norman, K. L. & Sarnow, P. Positive and negative modulation of viral and cellular mRNAs by liver-specific microRNA miR-122. Cold Spring Harb Symp Quant Biol 71, 369\u2013376, 10.1101\/sqb.2006.71.022 (2006).","journal-title":"Cold Spring Harb Symp Quant Biol"},{"key":"BFsrep23237_CR15","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1038\/nature07103","volume":"454","author":"JL Umbach","year":"2008","unstructured":"Umbach, J. L. et al. MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs. Nature 454, 780\u2013783, 10.1038\/nature07103 (2008).","journal-title":"Nature"},{"key":"BFsrep23237_CR16","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1126\/science.1187197","volume":"328","author":"D Cazalla","year":"2010","unstructured":"Cazalla, D., Yario, T., Steitz, J. A. & Steitz, J. Down-regulation of a host microRNA by a Herpesvirus saimiri noncoding RNA. Science 328, 1563\u20131566, 10.1126\/science.1187197 (2010).","journal-title":"Science"},{"key":"BFsrep23237_CR17","doi-asserted-by":"publisher","first-page":"2193","DOI":"10.1128\/JVI.02831-12","volume":"87","author":"C Li","year":"2013","unstructured":"Li, C. et al. Hepatitis B virus mRNA-mediated miR-122 inhibition upregulates PTTG1-binding protein, which promotes hepatocellular carcinoma tumor growth and cell invasion. J Virol 87, 2193\u20132205, 10.1128\/JVI.02831-12 (2013).","journal-title":"J Virol"},{"key":"BFsrep23237_CR18","doi-asserted-by":"publisher","first-page":"13370","DOI":"10.1128\/JVI.02130-13","volume":"87","author":"N Liu","year":"2013","unstructured":"Liu, N. et al. Hepatitis B virus inhibits apoptosis of hepatoma cells by sponging the MicroRNA 15a\/16 cluster. J Virol 87, 13370\u201313378, 10.1128\/JVI.02130-13 (2013).","journal-title":"J Virol"},{"key":"BFsrep23237_CR19","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.jhep.2015.09.013","volume":"64","author":"HW Liang","year":"2016","unstructured":"Liang, H. W. et al. Hepatitis B virus-human chimeric transcript HBx-LINE1 promotes hepatic injury via sequestering cellular microRNA-122. J Hepatol 64, 278\u2013291, 10.1016\/j.jhep.2015.09.013 (2016).","journal-title":"J Hepatol"},{"key":"BFsrep23237_CR20","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1073\/pnas.84.4.1005","volume":"84","author":"M Sells","year":"1987","unstructured":"Sells, M., Chen, M. & Acs, G. Production of hepatitis B virus particles in Hep G2 cells transfected with cloned hepatitis B virus DNA. Proc Natl Acad Sci USA 84, 1005\u20131009 (1987).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep23237_CR21","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1111\/j.1872-034X.2007.00262.x","volume":"38","author":"T Shin-I","year":"2008","unstructured":"Shin-I, T., Tanaka, Y., Tateno, Y. & Mizokami, M. Development and public release of a comprehensive hepatitis virus database. Hepatol Res 38, 234\u2013243, 10.1111\/j.1872-034X.2007.00262.x (2008).","journal-title":"Hepatol Res"},{"key":"BFsrep23237_CR22","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1016\/j.jhep.2011.11.017","volume":"56","author":"C Scisciani","year":"2012","unstructured":"Scisciani, C. et al. Transcriptional regulation of miR-224 upregulated in human HCCs by NF\u03baB inflammatory pathways. J Hepatol 56, 855\u2013861, 10.1016\/j.jhep.2011.11.017 (2012).","journal-title":"J Hepatol"},{"key":"BFsrep23237_CR23","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1093\/infdis\/jiq096","volume":"203","author":"P Yeung","year":"2011","unstructured":"Yeung, P. et al. Association of hepatitis B virus pre-S deletions with the development of hepatocellular carcinoma in chronic hepatitis B. J Infect Dis 203, 646\u2013654, 10.1093\/infdis\/jiq096 (2011).","journal-title":"J Infect Dis"},{"key":"BFsrep23237_CR24","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1111\/j.1478-3231.2012.02826.x","volume":"32","author":"JH Kao","year":"2012","unstructured":"Kao, J. H. et al. Fine mapping of hepatitis B virus pre-S deletion and its association with hepatocellular carcinoma. Liver Int 32, 1373\u20131381, 10.1111\/j.1478-3231.2012.02826.x (2012).","journal-title":"Liver Int"},{"key":"BFsrep23237_CR25","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.bbrc.2014.08.029","volume":"452","author":"N Ogura","year":"2014","unstructured":"Ogura, N., Watashi, K., Noguchi, T. & Wakita, T. Formation of covalently closed circular DNA in Hep38.7-Tet cells, a tetracycline inducible hepatitis B virus expression cell line. Biochem Biophys Res Commun 452, 315\u2013321, 10.1016\/j.bbrc.2014.08.029 (2014).","journal-title":"Biochem Biophys Res Commun"},{"key":"BFsrep23237_CR26","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1128\/AAC.41.8.1715","volume":"41","author":"SK Ladner","year":"1997","unstructured":"Ladner, S. K. et al. Inducible expression of human hepatitis B virus (HBV) in stably transfected hepatoblastoma cells: a novel system for screening potential inhibitors of HBV replication. Antimicrob Agents Chemother 41, 1715\u20131720 (1997).","journal-title":"Antimicrob Agents Chemother"},{"key":"BFsrep23237_CR27","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/j.jhep.2009.05.022","volume":"51","author":"M Levrero","year":"2009","unstructured":"Levrero, M. et al. Control of cccDNA function in hepatitis B virus infection. J Hepatol 51, 581\u2013592, 10.1016\/j.jhep.2009.05.022 (2009).","journal-title":"J Hepatol"},{"key":"BFsrep23237_CR28","doi-asserted-by":"publisher","first-page":"11916","DOI":"10.1128\/JVI.05373-11","volume":"85","author":"TB Lentz","year":"2011","unstructured":"Lentz, T. B. & Loeb, D. D. Roles of the envelope proteins in the amplification of covalently closed circular DNA and completion of synthesis of the plus-strand DNA in hepatitis B virus. J Virol 85, 11916\u201311927, 10.1128\/JVI.05373-11 (2011).","journal-title":"J Virol"},{"key":"BFsrep23237_CR29","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.1101\/gad.17352611","volume":"25","author":"BR Cullen","year":"2011","unstructured":"Cullen, B. R. Viruses and microRNAs: RISCy interactions with serious consequences. Genes Dev 25, 1881\u20131894, 10.1101\/gad.17352611 (2011).","journal-title":"Genes Dev"},{"key":"BFsrep23237_CR30","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.tcb.2008.07.007","volume":"18","author":"S Roush","year":"2008","unstructured":"Roush, S. & Slack, F. J. The let-7 family of microRNAs. Trends Cell Biol 18, 505\u2013516, 10.1016\/j.tcb.2008.07.007 (2008).","journal-title":"Trends Cell Biol"},{"key":"BFsrep23237_CR31","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/ng2003","volume":"39","author":"MS Kumar","year":"2007","unstructured":"Kumar, M. S., Lu, J., Mercer, K. L., Golub, T. R. & Jacks, T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet 39, 673\u2013677, 10.1038\/ng2003 (2007).","journal-title":"Nat Genet"},{"key":"BFsrep23237_CR32","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1101\/gad.1540407","volume":"21","author":"YS Lee","year":"2007","unstructured":"Lee, Y. S. & Dutta, A. The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev 21, 1025\u20131030, 10.1101\/gad.1540407 (2007).","journal-title":"Genes Dev"},{"key":"BFsrep23237_CR33","doi-asserted-by":"publisher","first-page":"2587","DOI":"10.1158\/0008-5472.CAN-08-0264","volume":"68","author":"B Boyerinas","year":"2008","unstructured":"Boyerinas, B. et al. Identification of let-7-regulated oncofetal genes. Cancer Res 68, 2587\u20132591, 10.1158\/0008-5472.CAN-08-0264 (2008).","journal-title":"Cancer Res"},{"key":"BFsrep23237_CR34","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1016\/j.cell.2011.10.039","volume":"147","author":"E Piskounova","year":"2011","unstructured":"Piskounova, E. et al. Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms. Cell 147, 1066\u20131079, 10.1016\/j.cell.2011.10.039 (2011).","journal-title":"Cell"},{"key":"BFsrep23237_CR35","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1038\/ng.392","volume":"41","author":"SR Viswanathan","year":"2009","unstructured":"Viswanathan, S. R. et al. Lin28 promotes transformation and is associated with advanced human malignancies. Nat Genet 41, 843\u2013848, 10.1038\/ng.392 (2009).","journal-title":"Nat Genet"},{"key":"BFsrep23237_CR36","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.ccr.2014.06.018","volume":"26","author":"LH Nguyen","year":"2014","unstructured":"Nguyen, L. H. et al. Lin28b is sufficient to drive liver cancer and necessary for its maintenance in murine models. Cancer Cell 26, 248\u2013261, 10.1016\/j.ccr.2014.06.018 (2014).","journal-title":"Cancer Cell"},{"key":"BFsrep23237_CR37","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.gene.2006.07.011","volume":"384","author":"Y Guo","year":"2006","unstructured":"Guo, Y. et al. Identification and characterization of lin-28 homolog B (LIN28B) in human hepatocellular carcinoma. Gene 384, 51\u201361, 10.1016\/j.gene.2006.07.011 (2006).","journal-title":"Gene"},{"key":"BFsrep23237_CR38","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1053\/j.gastro.2012.02.007","volume":"142","author":"TC Tseng","year":"2012","unstructured":"Tseng, T. C. et al. High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load. Gastroenterology 142, 1140\u20131149 e1143; quiz e1113-1144, 10.1053\/j.gastro.2012.02.007 (2012).","journal-title":"Gastroenterology"},{"key":"BFsrep23237_CR39","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1056\/NEJMoa013215","volume":"347","author":"HI Yang","year":"2002","unstructured":"Yang, H. I. et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med 347, 168\u2013174, 10.1056\/NEJMoa013215 (2002).","journal-title":"N Engl J Med"},{"key":"BFsrep23237_CR40","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1111\/hepr.12427","volume":"45","author":"E Orito","year":"2015","unstructured":"Orito, E. et al. Risk of hepatocellular carcinoma in cirrhotic hepatitis B virus patients during nucleoside\/nucleotide analog therapy. Hepatol Res 45, 872\u2013879, 10.1111\/hepr.12427 (2015).","journal-title":"Hepatol Res"},{"key":"BFsrep23237_CR41","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1016\/0092-8674(89)90770-8","volume":"59","author":"FV Chisari","year":"1989","unstructured":"Chisari, F. V. et al. Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice. Cell 59, 1145\u20131156 (1989).","journal-title":"Cell"},{"key":"BFsrep23237_CR42","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1002\/hep.1840200510","volume":"20","author":"I Toshkov","year":"1994","unstructured":"Toshkov, I., Chisari, F. V. & Bannasch, P. Hepatic preneoplasia in hepatitis B virus transgenic mice. Hepatology 20, 1162\u20131172 (1994).","journal-title":"Hepatology"},{"key":"BFsrep23237_CR43","doi-asserted-by":"publisher","first-page":"2313","DOI":"10.1007\/s007050050463","volume":"143","author":"K Takahashi","year":"1998","unstructured":"Takahashi, K., Akahane, Y., Hino, K., Ohta, Y. & Mishiro, S. Hepatitis B virus genomic sequence in the circulation of hepatocellular carcinoma patients: comparative analysis of 40 full-length isolates. Arch Virol 143, 2313\u20132326 (1998).","journal-title":"Arch Virol"},{"key":"BFsrep23237_CR44","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1002\/hep.25592","volume":"56","author":"T Pollicino","year":"2012","unstructured":"Pollicino, T. et al. Impact of hepatitis B virus (HBV) preS\/S genomic variability on HBV surface antigen and HBV DNA serum levels. Hepatology 56, 434\u2013443, 10.1002\/hep.25592 (2012).","journal-title":"Hepatology"},{"key":"BFsrep23237_CR45","doi-asserted-by":"publisher","first-page":"1972","DOI":"10.1136\/gutjnl-2015-309809","volume":"64","author":"M Nassal","year":"2015","unstructured":"Nassal, M. HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B. Gut 64, 1972\u20131984, 10.1136\/gutjnl-2015-309809 (2015).","journal-title":"Gut"},{"key":"BFsrep23237_CR46","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/ncomms1345","volume":"2","author":"K Kojima","year":"2011","unstructured":"Kojima, K. et al. MicroRNA122 is a key regulator of alpha-fetoprotein expression and influences the aggressiveness of hepatocellular carcinoma. Nat Commun 2, 338 (2011).","journal-title":"Nat Commun"},{"key":"BFsrep23237_CR47","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1002\/hep.26011","volume":"57","author":"A Takata","year":"2013","unstructured":"Takata, A. et al. MicroRNA-140 acts as a liver tumor suppressor by controlling NF-\u03baB activity by directly targeting DNA methyltransferase 1 (Dnmt1) expression. Hepatology 57, 162\u2013170, 10.1002\/hep.26011 (2013).","journal-title":"Hepatology"},{"key":"BFsrep23237_CR48","doi-asserted-by":"publisher","first-page":"7577","DOI":"10.1093\/nar\/gkv728","volume":"43","author":"T Yoshikawa","year":"2015","unstructured":"Yoshikawa, T. et al. ROCK inhibition enhances microRNA function by promoting deadenylation of targeted mRNAs via increasing PAIP2 expression. Nucleic Acids Res 43, 7577\u201389, 10.1093\/nar\/gkv728 (2015).","journal-title":"Nucleic Acids Res"},{"key":"BFsrep23237_CR49","doi-asserted-by":"publisher","first-page":"2553","DOI":"10.1038\/srep02553","volume":"3","author":"M Ohno","year":"2013","unstructured":"Ohno, M. et al. The flavonoid apigenin improves glucose tolerance through inhibition of microRNA maturation in miRNA103 transgenic mice. Sci Rep 3, 2553, 10.1038\/srep02553 (2013).","journal-title":"Sci Rep"},{"key":"BFsrep23237_CR50","doi-asserted-by":"publisher","first-page":"D140","DOI":"10.1093\/nar\/gkj112","volume":"34","author":"S Griffiths-Jones","year":"2006","unstructured":"Griffiths-Jones, S., Grocock, R. J., van Dongen, S., Bateman, A. & Enright, A. J. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res 34, D140\u2013144, 10.1093\/nar\/gkj112 (2006).","journal-title":"Nucleic Acids Res"},{"key":"BFsrep23237_CR51","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1016\/j.cell.2006.07.031","volume":"126","author":"KC Miranda","year":"2006","unstructured":"Miranda, K. C. et al. A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes. Cell 126, 1203\u20131217, 10.1016\/j.cell.2006.07.031 (2006).","journal-title":"Cell"},{"key":"BFsrep23237_CR52","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1007\/978-1-62703-484-5_13","volume":"1030","author":"D Cai","year":"2013","unstructured":"Cai, D. et al. A southern blot assay for detection of hepatitis B virus covalently closed circular DNA from cell cultures. Methods Mol Biol 1030, 151\u2013161, 10.1007\/978-1-62703-484-5_13 (2013).","journal-title":"Methods Mol Biol"},{"key":"BFsrep23237_CR53","doi-asserted-by":"publisher","first-page":"7950","DOI":"10.1074\/jbc.270.14.7950","volume":"270","author":"Y Higuchi","year":"1995","unstructured":"Higuchi, Y. & Linn, S. Purification of all forms of HeLa cell mitochondrial DNA and assessment of damage to it caused by hydrogen peroxide treatment of mitochondria or cells. J Biol Chem 270, 7950\u20137956 (1995).","journal-title":"J Biol Chem"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep23237","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep23237.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep23237.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T13:04:55Z","timestamp":1672837495000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep23237"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,16]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,9,2]]}},"alternative-id":["BFsrep23237"],"URL":"https:\/\/doi.org\/10.1038\/srep23237","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,16]]},"assertion":[{"value":"26 January 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 March 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"23237"}}