维基百科

miR-122

miR-122（英语：miR-122 microRNA）是一个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]，可调节脂肪酸代谢，也与肝细胞癌和丙型肝炎病毒复制有关[3]。

pri-miR-122
mir-122的二级结构和保守序列
识别符
代号 mir-122
Rfam RF00684
miRBase MI0000442
miRBase MIPF0000095
其他数据
RNA类型 Gene; miRNA
域 Eukaryota

表现与调控 编辑

miR-122于2002年克隆小鼠组织特异性miRNA的研究中发现，仅在肝脏细胞中表现[2]，后续实验在斑马鱼中也发现此miRNA于肝脏细胞中特异性地表现[4]。miR-122的表现在胚胎发育的过程中逐渐增加，成年人肝脏中有高达72%的miRNA为miR-122，为人体所有组织中表现量最大的miRNA[5]。人类的miR-122由18号染色体上的单一基因座编码，该基因座可转录产生miR-122的前驱物pri-miR-122（如右图所示），过程受HNF4A（英语：HNF4A）蛋白调控[6]；pri-miR-122可再被若干RNA酶切割产生长22nt的成熟miR-122[2][7]。成熟的miR-122之3′端会由GLD-2（英语：GLD-2）聚合酶加上一个A，可提升此miRNA的稳定度[8]。

有研究显示miR-122的表现也受昼夜节律蛋白Rev-ErbA alpha（英语：Rev-ErbA alpha）调控，因此其表现可能随生理时钟变化，且此miRNA也可调控PPARβ/δ（英语：Peroxisome proliferator-activated receptor delta）等数个昼夜节律蛋白之mRNA的基因表达[9]。

标的 编辑

miR-122可与许多mRNA结合以调控其基因表达，例如它可与CAT-1（英语：High affinity cationic amino acid transporter 1）mRNA的3'UTR结合以抑制其翻译，并使该mRNA被送入处理小体中；而当细胞面临特定逆境时，有另一蛋白HuR（英语：HuR）会从细胞核移至细胞质中，此蛋白也可与CAT-1之mRNA的3'UTR结合，可将该mRNA自处理小体中释出，并恢复其翻译，解除miR-122的抑制效果[10]。

miR-122的标的mRNA还有CD320（英语：CD320）、ALDOA与BCKDK（英语：BCKDK）等（给小鼠施予miR-122的抑制剂后，以mRNA微阵列（英语：Microarray）的实验分析发现），此miRNA控制许多和脂肪酸代谢相关的基因表达，受抑制剂抑制后会降低小鼠的血脂含量、促进肝脏代谢脂肪酸、并抑制肝脏合成脂肪酸和胆固醇，但具体机制尚未被完整阐明[11][12][13]。此外miR-122的标的mRNA还有HJV（英语：Hemojuvelin）与HFE（英语：HFE (gene)）等与铁代谢相关的基因[14]，以及SIRT6（英语：SIRT6）等与心血管疾病相关的基因[15]。

许多研究亦指出miR-122可调控许多参与干扰素（IFN）反应途径的基因，激活干扰素反应，增强抗病毒基因的表现[16][17][17][18][19][20]。有细胞实验结果显示miR-122过表达的细胞抗RNA病毒的干扰素等先天免疫反应较强[18]。

肝细胞癌患者肝细胞中的miR-122表现量经常较未患病者低，且低miR-122表现与较差的预后呈正相关[21][22]。细胞实验显示miR-122属于肿瘤抑制基因，其表现可抑制癌变，并增强索拉非尼与阿霉素等化疗药物的疗效[23][24]。已知ADAM10（英语：ADAM10）、IGF-1R、CCNG1（英语：CCNG1）与ADAM17（英语：ADAM17）等miR-122的标的基因都与肝细胞的癌变有关[23][24][25]。

调控丙型肝炎病毒 编辑

丙型肝炎病毒在肝细胞中的复制（英语：Viral replication）仰赖miR-122[26]，miR-122可与丙型肝炎病毒RNA5′端两个相邻的位点结合[27]，这两个位点在不同基因型的丙型肝炎病毒中均高度保守[28]。miRNA的功能一般为抑制基因表达，miR-122促进丙型肝炎病毒基因表达的机制尚不完全明朗，它可促进丙型肝炎病毒RNA的翻译，例如近期研究发现miR-122结合丙型肝炎病毒RNA后可能改变其二级结构，生成内部核糖体进入位点（IRES）而提升翻译[29]，此外可能还有其他机制参与促进病毒的复制[30][31]。miR-122促进丙型肝炎病毒RNA表现的机制应需AGO蛋白（英语：Argonaute）的参与[32]（但miR-122表现量够高时可能不需[33]），DDX6（英语：DDX6）等其他miRISC复合体的组成蛋白则非必须[34]。

Peginterferon alfa-2a（英语：Peginterferon alfa-2a）与利巴韦林等现有治疗丙型肝炎病毒的药物疗效有限且副作用强[35]，miR-122抑制剂为一种具潜力的药物，即以与miR-122互补的核酸和其结合以抑制其功能，但因低miR-122与肝细胞癌正相关，此类药物需经谨慎测试，且不应长期施用[18]。丹麦制药公司Santaris Pharma（英语：Santaris Pharma）开发中的抗丙型肝炎病毒药物Miravirsen（英语：Miravirsen）即为与miR-122互补的锁核酸[36]。

生物标记 编辑

miR-122被用作许多肝病的生物标记，血液中miR-122的含量可作为病毒、酒精或药物性的肝脏损伤[37][38][39]以及肝脏移植（英语：Liver transplantation）后发生排斥的指标[40][41]，其含量改变可能比转氨酶含量的改变更早发生，因此可用作肝脏损伤的早期指标[40][42]。此外miR-122还可用作纤维化、高血压、动脉粥状硬化等心血管疾病的早期指标[15]。

参考文献 编辑

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外部链接 编辑

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