非编码RNA调控自噬的分子机制及中药的干预作用

Molecular mechanisms of non-coding RNA regulating autophagy and interventional effects of Chinese herbal medicine

在哺乳动物细胞内,以长链非编码RNA(long non-coding RNA,lncRNA)和微小RNA(microRNA,miRNA)为代表的非编码RNA在调控自噬的上游发挥着重要作用。lncRNA和miRNA参与了自噬过程的各个阶段,包括起始、囊泡成核、自噬体成熟以及自噬体融合等。具有双向调控自噬作用的非编码RNA包括母系表达基因3(maternally expressed gene 3,MEG3),H19和miRNA-21(miR-21);具有抑制自噬作用的非编码RNA包括生长阻滞特异转录本5(growth arrest-specific transcript 5,GAS5),miRNA-34a(miR-34a)和miRNA-30a(miR-30a);具有促进自噬作用的非编码RNA包括转移相关的肺腺癌转录本1(metastasis associated lung adenocarcinoma transcript 1,MALAT1),miRNA-152(miR-152)和miRNA-24(miR-24)。非编码RNA调控自噬的作用具有条件性、多样性和复杂性的特点。近年来,国内外学者相继发现,白蔹素、丹酚酸B、丹皮酚等单味中药提取物和加味八珍方可以在体内外干预非编码RNA而调控自噬。最新的研究表明,植物源性短链非编码RNA(small non-coding RNA,sncRNA)作为中药的有效成分之一可以直接进入循环血液和内脏而跨界调控人类基因表达。此外,大黄酸、金丝桃苷以及虫草菌丝均能在体内外通过调控自噬相关信号通路而干预肾小管上皮细胞自噬,减轻肾脏损伤和肾脏衰老,其部分药理机制可能与miR-34a通路介导有关。总之,针对肿瘤、免疫性疾病、代谢性疾病以及神经退行性疾病等临床常见疾病而揭示非编码RNA(lncRNA和miRNA)调控自噬的分子机制,这是建立精准治疗策略和阐明中药药理作用的必由之路。

Long non-coding RNAs(lncRNAs)and microRNAs(miRNAs),as members of the non-coding RNA family,play important roles in upstream processes that regulate autophagy in mammalian cells.LncRNA and miRNA participate in various phases of the process of autophagy,including initiation,vesicle nucleation,autophagosome maturation and autophagosome fusion.Some non-coding RNAs exert bidirectional regulatory functions in the process of autophagy,include the maternally expressed gene 3(MEG3),H19 and miR-21,whereas others either inhibit autophagy(including GAS5,miR-34 a and miR-30 a)or promote autophagy(including MALAT1,miR-152 and miR-24).The regulation of autophagy by non-coding RNAs has characteristics of conditionality,diversity and complexity.In recent years,researchers at home and abroad have constantly found that some extracts from the individual Chinese herbal medicine(CHM)such as ampelopsin,salvianolic acid B and paeonol,as well as the Chinese herbal compound named Eight Ingredients Decoction,can regulate autophagy by interacting with non-coding RNA in vitro and in vivo.The latest studies have shown that plant-derived small non-coding RNAs(sncRNAs)as one of the active ingredients of CHMs can directly enter the bloodstream and internal organs to regulate gene expressions in humans.In addition,it has been reported that rhein,hyperoside and mycelium of Cordyceps sinensis all can modulate autophagy in renal tubular epithelial cell via regulating the autophagy-related signaling pathways in vivo and in vitro to reduce renal damage and aging,which is likely mediated by the miR-34 a pathway.In summary,the understanding of molecular mechanisms underlying the regulation of autophagy by non-coding RNAs(such as lncRNAs and miRNAs)is essential and required to develop new strategies for the treatments and managements of tumors,immune diseases,metabolic diseases,neurodegenerative diseases and other common diseases and decipher pharmacologic actions of CHMs.