miR-122

本页使用了标题或全文手工转换
维基百科，自由的百科全书
pri-miR-122
mir-122的二級結構和保守序列
识别符
代号 mir-122
Rfam RF00684
miRBase MI0000442
miRBase MIPF0000095
其他数据
RNA类型 Gene; miRNA
域 Eukaryota

miR-122（英語：miR-122 microRNA）是一個miRNA，在脊椎动物中保守，但不存在无脊椎动物基因组中，且无旁系同源物[1]。miR-122在肝脏中高表达[2]，可调节脂肪酸代謝，也与肝細胞癌和丙型肝炎病毒复制有关[3]。

表現與調控

miR-122於2002年克隆小鼠組織特異性miRNA的研究中發現，僅在肝臟細胞中表現[2]，後續實驗在斑馬魚中也發現此miRNA於肝臟細胞中特異性地表現[4]。miR-122的表現在胚胎發育的過程中逐漸增加，成年人肝臟中有高達72%的miRNA為miR-122，為人體所有組織中表現量最大的miRNA[5]。人類的miR-122由18號染色體上的單一基因座編碼，該基因座可轉錄產生miR-122的前驅物pri-miR-122（如右圖所示），過程受HNF4A（英语：HNF4A）蛋白調控[6]；pri-miR-122可再被若干RNA酶切割產生長22nt的成熟miR-122[2][7]。成熟的miR-122之3′端會由GLD-2（英语：GLD-2）聚合酶加上一個A，可提升此miRNA的穩定度[8]。

有研究顯示miR-122的表現也受晝夜節律蛋白Rev-ErbA alpha（英语：Rev-ErbA alpha）調控，因此其表現可能隨生理時鐘變化，且此miRNA也可調控PPARβ/δ（英语：Peroxisome proliferator-activated receptor delta）等數個晝夜節律蛋白之mRNA的基因表現[9]。

標的

miR-122可與許多mRNA結合以調控其基因表現，例如它可與CAT-1（英语：High affinity cationic amino acid transporter 1）mRNA的3'UTR結合以抑制其轉譯，並使該mRNA被送入處理小體中；而當細胞面臨特定逆境時，有另一蛋白HuR（英语：HuR）會從細胞核移至細胞質中，此蛋白也可與CAT-1之mRNA的3'UTR結合，可將該mRNA自處理小體中釋出，並恢復其轉譯，解除miR-122的抑制效果[10]。

miR-122的標的mRNA還有CD320（英语：CD320）、ALDOA與BCKDK（英语：BCKDK）等（給小鼠施予miR-122的抑制劑後，以mRNA微陣列（英语：Microarray）的實驗分析發現），此miRNA控制許多和脂肪酸代謝相關的基因表現，受抑制劑抑制後會降低小鼠的血脂含量、促進肝臟代謝脂肪酸、並抑制肝臟合成脂肪酸和膽固醇，但具體機制尚未被完整闡明[11][12][13]。此外miR-122的標的mRNA還有HJV（英语：Hemojuvelin）與HFE（英语：HFE (gene)）等與鐵代謝相關的基因[14]，以及SIRT6（英语：SIRT6）等與心血管疾病相關的基因[15]。

許多研究亦指出miR-122可調控許多參與干擾素（IFN）反應途徑的基因，活化干擾素反應，增強抗病毒基因的表現[16][17][17][18][19][20]。有細胞實驗結果顯示miR-122過表達的細胞抗RNA病毒的干擾素等先天免疫反應較強[18]。

肝細胞癌患者肝細胞中的miR-122表現量經常較未患病者低，且低miR-122表現與較差的預後呈正相關[21][22]。細胞實驗顯示miR-122屬於腫瘤抑制基因，其表現可抑制癌變，並增強索拉非尼與阿黴素等化療藥物的療效[23][24]。已知ADAM10（英语：ADAM10）、IGF-1R、CCNG1（英语：CCNG1）與ADAM17（英语：ADAM17）等miR-122的標的基因都與肝細胞的癌變有關[23][24][25]。

調控C型肝炎病毒

C型肝炎病毒在肝細胞中的複製（英语：Viral replication）仰賴miR-122[26]，miR-122可與C型肝炎病毒RNA5′端兩個相鄰的位點結合[27]，這兩個位點在不同基因型的C型肝炎病毒中均高度保守[28]。miRNA的功能一般為抑制基因表現，miR-122促進C型肝炎病毒基因表現的機制尚不完全明朗，它可促進C型肝炎病毒RNA的轉譯，例如近期研究發現miR-122結合C型肝炎病毒RNA後可能改變其二級結構，生成內部核糖體進入位點（IRES）而提升轉譯[29]，此外可能還有其他機制參與促進病毒的複製[30][31]。miR-122促進C型肝炎病毒RNA表現的機制應需AGO蛋白（英语：Argonaute）的參與[32]（但miR-122表現量夠高時可能不需[33]），DDX6（英语：DDX6）等其他miRISC複合體的組成蛋白則非必須[34]。

Peginterferon alfa-2a（英语：Peginterferon alfa-2a）與利巴韋林等現有治療C型肝炎病毒的藥物療效有限且副作用強[35]，miR-122抑制劑為一種具潛力的藥物，即以與miR-122互補的核酸和其結合以抑制其功能，但因低miR-122與肝細胞癌正相關，此類藥物需經謹慎測試，且不應長期施用[18]。丹麥製藥公司Santaris Pharma（英语：Santaris Pharma）開發中的抗C型肝炎病毒藥物Miravirsen（英语：Miravirsen）即為與miR-122互補的鎖核酸[36]。

生物標記

miR-122被用作許多肝病的生物標記，血液中miR-122的含量可作為病毒、酒精或藥物性的肝臟損傷[37][38][39]以及肝臟移植（英语：Liver transplantation）後發生排斥的指標[40][41]，其含量改變可能比轉氨酶含量的改變更早發生，因此可用作肝臟損傷的早期指標[40][42]。此外miR-122還可用作纖維化、高血壓、動脈粥狀硬化等心血管疾病的早期指標[15]。

参考文献

  1. ^ miRBase. [2022-06-02]. （原始内容存档于2017-05-09）. 
  2. ^ 2.0 2.1 2.2 Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. Identification of tissue-specific microRNAs from mouse.. Curr Biol. 2002, 12 (9): 735–739. PMID 12007417. S2CID 7901788. doi:10.1016/S0960-9822(02)00809-6. 
  3. ^ Cao, M; Isaac, R; Yan, W; Ruan, X; Jiang, L; Wan, Y; Wang, J; Wang, E; Caron, C; Neben, S; Drygin, D; Pizzo, DP; Wu, X; Liu, X; Chin, AR; Fong, MY; Gao, Z; Guo, K; Fadare, O; Schwab, RB; Yuan, Y; Yost, SE; Mortimer, J; Zhong, W; Ying, W; Bui, JD; Sears, DD; Olefsky, JM; Wang, SE. Cancer-cell-secreted extracellular vesicles suppress insulin secretion through miR-122 to impair systemic glucose homeostasis and contribute to tumour growth.. Nature cell biology. 2022-05-30. PMID 35637408. doi:10.1038/s41556-022-00919-7. 
  4. ^ Wienholds E, Kloosterman WP, Miska E, Alvarez-Saavedra E, Berezikov E, de Bruijn E, Horvitz HR, Kauppinen S, Plasterk RH. MicroRNA expression in zebrafish embryonic development. Science. 2005, 309 (5732): 310–311. Bibcode:2005Sci...309..310W. PMID 15919954. S2CID 38939571. doi:10.1126/science.1114519. 
  5. ^ Chang J, Nicolas E, Marks D, Sander C, Lerro A, Buendia MA, xu C, Mason WS, Moloshok T, Bort R, Zaret KS, Taylor JM. 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. 2004, 1 (2): 106–113. PMID 17179747. S2CID 2956276. doi:10.4161/rna.1.2.1066. 
  6. ^ 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. Positive regulation of hepatic miR-122 expression by HNF4α. Journal of Hepatology. 2011, 55 (3): 602–611. PMID 21241755. doi:10.1016/j.jhep.2010.12.023. 
  7. ^ Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V. Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation.. Genome Biol. 2004, 5 (3): R13. PMC 395763 可免费查阅. PMID 15003116. doi:10.1186/gb-2004-5-3-r13. 
  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. 2009, 23 (4): 433–438. PMC 2648654 可免费查阅. PMID 19240131. doi:10.1101/gad.1761509. 
  9. ^ Gatfield D, Le Martelot G, Vejnar CE, Gerlach D, Schaad O, Fleury-Olela F, Ruskeepää AL, Oresic M, Esau CC, Zdobnov EM, Schibler U. Integration of microRNA miR-122 in hepatic circadian gene expression.. Genes Dev. 2009, 23 (11): 1313–1326. PMC 2701584 可免费查阅. PMID 19487572. doi:10.1101/gad.1781009. 
  10. ^ 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. June 2006, 125 (6): 1111–1124. PMID 16777601. S2CID 18353167. doi:10.1016/j.cell.2006.04.031. 
  11. ^ Krützfeldt, Jan; Rajewsky, Nikolaus, Braich, Ravi, Rajeev, Kallanthottathil G., Tuschl, Thomas, Manoharan, Muthiah, Stoffel, Markus. Silencing of microRNAs in vivo with 'antagomirs'. Nature. December 2005, 438 (7068): 685–689. Bibcode:2005Natur.438..685K. PMID 16258535. S2CID 4414240. doi:10.1038/nature04303. 
  12. ^ 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. 2006, 3 (2): 87–98. PMID 16459310. doi:10.1016/j.cmet.2006.01.005. 
  13. ^ Elmén J, Lindow M, Silahtaroglu A, et al. 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. March 2008, 36 (4): 1153–1162. PMC 2275095 可免费查阅. PMID 18158304. doi:10.1093/nar/gkm1113. 
  14. ^ 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. 2011, 121 (4): 1386–1396. PMC 3069782 可免费查阅. PMID 21364282. doi:10.1172/JCI44883. 
  15. ^ 15.0 15.1 Liu Y, Song JW, Lin JY, Miao R, Zhong JC. Roles of MicroRNA-122 in Cardiovascular Fibrosis and Related Diseases.. Cardiovasc Toxicol. 2020, 20 (5): 463–473. PMC 7451782 可免费查阅. PMID 32856216. doi:10.1007/s12012-020-09603-4. 
  16. ^ Wilson, JA; Sagan, SM. Hepatitis C virus and human miR-122: insights from the bench to the clinic. Current Opinion in Virology. August 2014, 7: 11–18. PMID 24721497. doi:10.1016/j.coviro.2014.03.005. 
  17. ^ 17.0 17.1 Forster, SC; Tate, MD; Hertzog, PJ. MicroRNA as Type I Interferon-Regulated Transcripts and Modulators of the Innate Immune Response. Frontiers in Immunology. 2015, 6: 334. PMC 4495342 可免费查阅. PMID 26217335. doi:10.3389/fimmu.2015.00334 可免费查阅. 
  18. ^ 18.0 18.1 18.2 Israelow, B; Narbus, CM; Sourisseau, M; Evans, MJ. HepG2 cells mount an effective antiviral interferon-lambda based innate immune response to hepatitis C virus infection. Hepatology. October 2014, 60 (4): 1170–1179. PMC 4176518 可免费查阅. PMID 24833036. doi:10.1002/hep.27227. 
  19. ^ 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. MiR-122 modulates type I interferon expression through blocking suppressor of cytokine signaling 1. The International Journal of Biochemistry & Cell Biology. April 2013, 45 (4): 858–865. PMID 23348614. doi:10.1016/j.biocel.2013.01.008. 
  20. ^ Xiong, Y; Zhang, C; Yuan, J; Zhu, Y; Tan, Z; Kuang, X; Wang, X. 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. March 2015, 11 (3): 1733–1737. PMC 4270330 可免费查阅. PMID 25377467. doi:10.3892/mmr.2014.2897. 
  21. ^ 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. 2006, 99 (3): 671–678. PMC 3033198 可免费查阅. PMID 16924677. doi:10.1002/jcb.20982. 
  22. ^ 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. October 2009, 28 (40): 3526–3536. PMC 3492882 可免费查阅. PMID 19617899. doi:10.1038/onc.2009.211. 
  23. ^ 23.0 23.1 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. 2009, 284 (46): 32015–32027. PMC 2797273 可免费查阅. PMID 19726678. doi:10.1074/jbc.M109.016774 可免费查阅. 
  24. ^ 24.0 24.1 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. July 2009, 69 (14): 5761–5767. PMID 19584283. doi:10.1158/0008-5472.CAN-08-4797. 
  25. ^ 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. May 2009, 49 (5): 1571–1582. PMID 19296470. S2CID 12797340. doi:10.1002/hep.22806. 
  26. ^ Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA.. Science. 2005, 309 (5740): 1577–1581. Bibcode:2005Sci...309.1577J. PMID 16141076. S2CID 13405582. doi:10.1126/science.1113329. 
  27. ^ Jopling, L.; Schütz, S.; Sarnow, P. Position-dependent function for a tandem microRNA miR-122-binding site located in the hepatitis C virus RNA genome. Cell Host & Microbe. Jul 2008, 4 (1): 77–85. ISSN 1931-3128. PMC 3519368 可免费查阅. PMID 18621012. doi:10.1016/j.chom.2008.05.013. 
  28. ^ 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. Cellular cofactors affecting hepatitis C virus infection and replication.. Proc Natl Acad Sci U S A. 2007, 104 (31): 12884–12889. Bibcode:2007PNAS..10412884R. PMC 1937561 可免费查阅. PMID 17616579. doi:10.1073/pnas.0704894104 可免费查阅. 
  29. ^ Chahal J, Gebert LFR, Gan HH, Camacho E, Gunsalus KC, MacRae IJ; et al. miR-122 and Ago interactions with the HCV genome alter the structure of the viral 5' terminus.. Nucleic Acids Res. 2019, 47 (10): 5307–5324. PMC 6547439 可免费查阅. PMID 30941417. doi:10.1093/nar/gkz194. 
  30. ^ Henke JI, Goergen D, Zheng J, Song Y, Schüttler CG, Fehr C, Jünemann C, Niepmann M. microRNA-122 stimulates translation of hepatitis C virus RNA.. EMBO J. 2008, 27 (24): 3300–3310. PMC 2586803 可免费查阅. PMID 19020517. doi:10.1038/emboj.2008.244. 
  31. ^ Jangra RK, Yi M, Lemon SM. Regulation of hepatitis C virus translation and infectious virus production by the microRNA miR-122.. J Virol. 2010, 84 (13): 6615–6625. PMC 2903297 可免费查阅. PMID 20427538. doi:10.1128/JVI.00417-10. 
  32. ^ Wilson JA, Zhang C, Huys A, Richardson CD. Human Ago2 is required for efficient miR-122 regulation of HCV RNA accumulation and translation.. J Virol. 2010, 85 (5): 2342–2350. PMC 3067765 可免费查阅. PMID 21177824. doi:10.1128/JVI.02046-10. 
  33. ^ 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. 2011, 108 (8): 3193–3198. Bibcode:2011PNAS..108.3193M. PMC 3044371 可免费查阅. PMID 21220300. doi:10.1073/pnas.1012464108 可免费查阅. 
  34. ^ Jangra RK, Yi M, Lemon SM. DDX6 (Rck/p54) is required for efficient hepatitis C virus replication but not for internal ribosome entry site-directed translation.. J Virol. 2010, 84 (13): 6810–6824. PMC 2903299 可免费查阅. PMID 20392846. doi:10.1128/JVI.00397-10. 
  35. ^ 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. IL28B genotype is associated with differential expression of intrahepatic interferon-stimulated genes in patients with chronic hepatitis C. Hepatology. December 2010, 52 (6): 1888–1896. PMC 3653303 可免费查阅. PMID 20931559. doi:10.1002/hep.23912. 
  36. ^ Titze-de-Almeida, R; David, C; Titze-de-Almeida, SS. The Race of 10 Synthetic RNAi-Based Drugs to the Pharmaceutical Market. Pharmaceutical Research. July 2017, 34 (7): 1339–1363. PMID 28389707. S2CID 4925216. doi:10.1007/s11095-017-2134-2. 
  37. ^ Wang, Kai; Shile Zhang, Bruz Marzolf, Pamela Troisch, Amy Brightman, Zhiyuan Hu, Leroy E. Hood, and David J. Galas. Circulating microRNAs, potential biomarkers for drug-induced liver injury. PNAS. 17 March 2009, 106 (11): 4402–4407. Bibcode:2009PNAS..106.4402W. PMC 2657429 可免费查阅. PMID 19246379. doi:10.1073/pnas.0813371106 可免费查阅. 
  38. ^ 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. Serum miR-122 as a biomarker of necroinflammation in patients with chronic hepatitis C virus infection. American Journal of Gastroenterology. 24 May 2011, 106 (9): 1663–1669. PMID 21606975. S2CID 21212744. doi:10.1038/ajg.2011.161. hdl:10033/214238. 
  39. ^ 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. Hepatocyte-derived microRNAs as sensitive serum biomarkers of hepatocellular injury in Labrador retrievers. The Veterinary Journal. 2016, 211: 75–81. PMID 27021912. doi:10.1016/j.tvjl.2016.01.010. 
  40. ^ 40.0 40.1 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. Hepatocyte-derived microRNAs as serum biomarkers of hepatic injury and rejection after liver transplantation. Liver Transplantation. 2012, 18 (3): 290–297. PMID 21932376. S2CID 6705422. doi:10.1002/lt.22438. 
  41. ^ 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.
  42. ^ 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. The release of microRNA-122 during liver preservation is associated with early allograft dysfunction and graft survival after transplantation. Liver Transplantation. 2017, 23 (7): 946–956. PMID 28388830. S2CID 4716863. doi:10.1002/lt.24766. 

外部链接

取自“https://zh.wikipedia.org/w/index.php?title=MiR-122&oldid=73112983”