外泌体长链非编码RNA对脂代谢调控机制的研究进展

doi:10.16431/j.cnki.1671-7236.2020.04.007

摘要/Abstract

摘要： 外泌体（exosomes）是一类由细胞分泌并且可远距离传递生物信息的纳米级胞外囊泡。它通过细胞分泌释放，在体液中传播，最后被其他细胞吞噬以达到传递生物信息的作用。脂类代谢一直是生命科学研究领域的热点，虽然影响脂质代谢的长链非编码RNA（lncRNA）很多，但外泌体中影响脂质代谢的lncRNA研究却相对较少。基于这个原因，对于外泌体源lncRNA的研究就十分必要。作为外泌体所携带的重要遗传物质之一，lncRNA是一类长度 > 200 nt的RNA分子，行使着诸如转录激活、染色质修饰等许多重要的生物功能。文章介绍了外泌体源lncRNA的生物学特点，列举了外泌体源lncRNA通过不同的分子机制来直接或间接的对脂质代谢产生影响的实例，分析了外泌体源lncRNA由于表达异常所导致的脂类代谢疾病，并且举例说明了外泌体源lncRNA作为生物标记的原理，最后对外泌体源lncRNA可作为家畜脂肪沉积生物标记功能的前景做了展望。如果在未来的研究中有更多的外泌体源lncRNA被检出，并足够对脂类代谢异常情况进行标记的话，那么对于预测和调控家畜脂肪沉积无疑会产生积极的意义。

关键词: 外泌体; 长链非编码RNA(lncRNA); 脂代谢

Abstract: Exosomes are a kind of nanometer extracellular vesicle secreted by cells and they are able to transmit biological information in a long distance.Exosomes are secreted and released by cells,then transmitted in body fluids,finally swallowed in another cells to transmit biological information.Lipid metabolism has always been a hotspot of the field of life science research.Although there are many lncRNAs affecting lipid metabolism,there are relatively few lncRNAs studies affecting lipid metabolism in exosomes.For this reason,the study of exosomal-lncRNAs shows it’s necessity.As one of the important genetic material carried by the exosomes,the long non-coding RNAs are a kind of RNA molecule of which length for more than 200 nt,and perform many important biological functions such as transcriptional activation,chromatin modification and so on.In this paper,the biological characteristics of the exosomal-lncRNAs have been introduced,and the examples of the effect of exosomal-lncRNAs on lipid metabolism by different molecular mechanisms have been listed.The lipid metabolism disease caused by the abnormal expression of exosomal-lncRNAs has analyzed,and the principle of the exosomal-lncRNA acted as lipid metabolism disease’s biomarker has also illustrated.Finally,the prospect of exosomal-lncRNA as a biomarker for animal fat deposition has prospected.If more exosome-derived lncRNAs are detected in the future research,and it’s sufficiently to label abnormal conditions of lipid metabolism,there will undoubtedly be positive implications for the prediction and regulation of fat deposition in livestock.

Key words: exosomes; long non-coding RNA (lncRNA); lipid metabolism

中图分类号:

张珈溯, 夏广军, 尹宝珍, 张洛萌, 邵静, 耿春银. 外泌体长链非编码RNA对脂代谢调控机制的研究进展[J]. 中国畜牧兽医, 2020, 47(4): 1028-1034.

ZHANG Jiasu, XIA Guangjun, YIN Baozhen, ZHANG Luomeng, SHAO Jing, GENG Chunyin. Research Progress on the Regulation Mechanism of Exosomal lncRNA on Lipid Metabolism[J]. China Animal Husbandry and Veterinary Medicine, 2020, 47(4): 1028-1034.

参考文献

[1] TRAMS E G,LAUTER C J,SALEM N,et al.Exfoliation of membrane ecto-enzymes in the form of micro-vesicles[J].Biochimica et Biophysica Acta,1981,645(1):63-70.
[2] ZHANG Y,YU M,TIAN W.Physiological and pathological impact of exosomes of adipose tissue[J].Cell Proliferation,2016,49(1):3-13.
[3] CRUZ C,HOUSELY J.Protocols for northern analysis of exosome substrates and other noncoding RNAs[J].Methods in Molecular Biology,2020,2062:83-103.
[4] 甘露.内质网应激调控机体脂肪代谢稳态的分子机制研究[D].西安:西北农林科技大学,2018. GAN L.A study on the effects of ER stress on lipid metabolism homeostasis and the underlying mechanism[D].Xi'an:Northwest A&F University,2018.(in Chinese)
[5] HOCK A,MIYAKE H,LI B,et al.Breast milk-derived exosomes promote intestinal epithelial cell growth[J].Journal of Pediatric Surgery,2017,52(5):755-759.
[6] QU M,LIN Q,HUANG L,et al.Dopamine-loaded blood exosomes targeted to brain for better treatment of Parkinson's disease[J].Journal of Controlled Release,2018,287:156-166.
[7] LV C Y,ZHAO Z Y,YANG T L,et al.Liquid biopsy biomarkers of renal interstitial fibrosis based on urinary exosome[J].Experimental and Molecular Pathology,2018,105(2):223-228.
[8] DENG Z B,POLIAKOV A,HARDYR W,et al.Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance[J].Diabetes,2009,58(11):2498-2505.
[9] 张潜英,李虎,李常银,等.骨骼肌组织来源的外泌体促进骨骼肌干细胞增殖并抑制其分化[J].中国细胞生物学学报,2018,40(7):1171-1178. ZHANG Q Y,LI H,LI C Y,et al.Skeletal muscle derived-exosome promotes proliferation and inhibits differentiation of muscle stem cells[J].Chinese Journal of Cell Biology,2018,40(7):1171-1178.(in Chinese)
[10] LIN R,WANG S,ZHAO R C.Exosomes from human adipose-derived mesenchymal stem cells promote migration through Wnt signaling pathway in a breast cancer cell model[J].Molecular and Cellular Biochemistry,2013,383(1-2):13-20.
[11] FONTANA S,SAIEVA L,TAVERNA S,et al.Contribution of proteomics to understanding the role of tumor-derived exosomes in cancer progression:State of the art and new perspectives[J].Proteomics,2013,13,1581-1594.
[12] 于红.表观遗传学:生物细胞非编码RNA调控的研究进展[J].遗传,2009,31(11):1077-1086. YU H.Epigenetics:Advances of non-coding RNAs regulation in mammalian cells[J].Hereditas,2009,31(11):1077-1086.(in Chinese)
[13] GEZER U,ÖZGUR E,CETINKAYA M,et al.Long non-coding RNAs with low expression levels in cells are enriched in secreted exosomes[J].Cell Biology International,2014,38(9):1076.
[14] SALMENA L,POLISENO L,TAY Y,et al.A ceRNA hypothesis:The rosetta stone of a hidden RNA language[J].Cell,2011,146(3):353-358.
[15] QI P,ZHOU X Y,DU X.Circulating long non-coding RNAs in cancer:Current status and future perspectives[J].Molecular Cancer,2016,15(1):39.
[16] 任潇凡,李志花.外泌体lncRNA CCAT1在胰腺癌中的表达及其临床意义[J].岭南现代临床外科,2019,19(1):23-27. REN X F,LI Z H.Expression and clinical significance of exosomal long non-coding RNA CCATl in pancreatic cancer[J].Lingnan Modern Clinical Surgery,2019,19(1):23-27.(in Chinese)
[17] NOJIMA H,FREEMAN C M,SCHUSTER R M,et al.Hepatocyte exosomes mediate liver repair and regeneration via sphingosine-1-phosphate[J].Journal of Hepatology,2015,64:60-68.
[18] 陈燕,黄亚洲,陈慧,等.长非编码RNA RLM通过影响AMPK的磷酸化调节HepG2细胞中的脂质沉积[J].中国生物化学与分子生物学报,2019,35(7):757-764. CHEN Y,HUANG Y Z,CHEN H,et al.Long non-coding RNA RLM regulates the lipid deposition in HepG2 cells by affecting phosphorylation of AMPK[J].Chinese Journal of Biochemistry and Molecular Biology,2019,35(7):757-764.(in Chinese)
[19] SMITS G,MUNGALLA J,GRIFFITHS J S,et al.Conservation of the H19 non-coding RNA and H19-IGF2 imprinting mechanism in therians[J].Nature Genetics,2008,40(8):971-976.
[20] HARK A T,SCHOENHERR C J,KATZ D J,et al.CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus[J].Nature,2000,405(6785):486-489.
[21] JALALI S,BHARTIYA D,LALWANI M K,et al.Systematic transcriptome wide analysis of lncRNA-mi-RNA interactions[J].PLoS One,2017,8(2):e53823.
[22] YAO X B,LIU C,LIU C Y,et al.lncRNA SNHG7 sponges miR-425 to promote proliferation,migration,and invasion of hepatic carcinoma cells via Wnt/β-catenin/EMT signalling pathway[J].Cell Biochemistry and Function,2019,37(7),525-533.
[23] TONG Y X,WANG M S,DAI Y N,et al.lncRNA HOXA-AS3 sponges miR-29c to facilitate cell proliferation,metastasis,and EMT process and activate the MEK/ERK signaling pathway in hepatocellular carcinoma[J].Human Gene Therapy,2018,30(3):266.
[24] LIU J Y,YAO J,LI X M,et al.Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus[J].Cell Death&Disease,2014,5(10):e1506.
[25] YAN B,TAO Z F,LI X M,et al.Aberrant expression of long non-coding RNAs in early diabetic retinopathy[J].Investigative Opthalmology&Visual Science,2014,55(2):941.
[26] GU Y,XIAO X,YANG S.lncRNA MALAT1 acts as an oncogene in multiple myeloma through sponging miR-509-5p to modulate FOXP1 expression[J].Oncotarget,2017,8(60):101984-101993.
[27] 黄思霞.Wntless调控毛囊发育,毛发循环和表皮代谢及Foxp1调节棕色脂肪形成与功能的机理研究[D].上海:上海交通大学,2015. HUANG S X.The study of the roles of Wntless in hair follicle development,hair cicling and epidermal homeostasis and the function of Foxp1 in brown adipose tissue formation and function[D].Shanghai:Shanghai Jiaotong University,2015.(in Chinese)
[28] LI P,ZHANG X,WANG L,et al.lncRNA HOTAIR contributes to 5FU resistance through suppressing miR-218 and activating NF-κB/TS signaling in colorectal cancer[J].Molecular Therapy,2017,8:356-369.
[29] XU B M,XIAO L,KANG C M,et al.lncRNA AC096664.3/PPAR-γ/ABCG1-dependent signal transduction pathway contributes to the regulation of cholesterol homeostasis[J].Journal of Cellular Biochemistry,2019,120(4):1002.
[30] ZHUO X,WU Y,YANG Y J,et al.lncRNA AK094457 promotes AngII-mediated hypertension and endothelial dysfunction through suppressing of activation of PPARγ[J].Life Sciences,2019,233:116745.
[31] CHEN J,LIU Y,LU S,et al.The role and possible mechanism of lncRNA U90926 in modulating 3T3-L1 preadipocyte differentiation[J].International Journal of Obesity,2017,41(2):299-308.
[32] LIU W,MA C,YANG B,et al.lncRNA Gm15290 sponges miR-27b to promote PPARγ-induced fat deposition and contribute to body weight gain in mice[J].Biochemical and Biophysical Research Communications,2017:493(3):1168-1175.
[33] 于洋.脂肪源性含miR-27a外泌体通过抑制PPARγ诱导骨骼肌胰岛素抵抗的作用机制研究[D].吉林:吉林大学,2018. YU Y.Adiposyte-derived exosomal miR-27a induces insulin resistance in skeletal muscle through repressing of PPARγ[D].Jilin:Jilin University,2018.(in Chinese)
[34] QIU Q Y,ZHANG B L,ZHANG M Z,et al.Combined influence of insulin resistance and inflammatory biomarkers on type 2 diabetes:A population-based prospective cohort study of inner mongolians in China[J].Biomedical and Environmental Sciences,2018,31(4):300-305.
[35] MORÁN I,AKERMAN I,VAN DE BUNT M,et al.Human β cell transcriptome analysis uncovers lnc-RNAs that are tissue-specific,dynamically regulated,and abnormally expressed in type 2 diabetes[J].Cell Metabolism,2012,16(4),435-448.
[36] ARNES L,AKERMAN I,BALDERES D A,et al.βlinc1 encodes a long noncoding RNA that regulates islet β-cell formation and function[J].Genes&Development,2016,30(5):502-507.
[37] BIN X,ISABELLE G,HONGZHI M,et al.Multiple roles for the non-coding RNA SRA in regulation of adipogenesis and insulin sensitivity[J].PLoS One,2010,5(12):e14199.
[38] SHANNON L,RUICHUAN X,ISABELLE G,et al.SRA regulates adipogenesis by modulating p38/JNK phosphorylation and stimulating insulin receptor gene expression and downstream signaling[J].PLoS One,2014,9(4):e95416.
[39] JIN F,WANG N,ZHU Y,et al.Downregulation of long noncoding RNA Gas5 affects cell cycle and insulin secretion in mouse pancreatic β cells[J].Cellular Physiology and Biochemistry,2017,43(5):2062-2073.
[40] YING W,RIOPEL M,BANDYOPADHYAY G,et al.Adipose tissue macrophage-derived exosomal miRNAs can modulate in vivo and in vitro insulin sensitivity[J].Cell,2017,171(2):372.
[41] CHANDRAKUMAR S,PARAMASIVAM P,VISWANATHAN M,et al.Linking a role of lncRNAs (long non-coding RNAs) with insulin resistance,accelerated senescence,and inflammation in patients with type 2 diabetes[J].Human Genomics,2018,12(1):41.
[42] CHEN J,KE S,ZHONG L,et al.Long noncoding RNA MALAT1 regulates generation of reactive oxygen species and the insulin responses in male mice[J].Biochemical Pharmacology,2018,152:94-103.
[43] CHEN G,YU D,NIAN X,et al.lncRNA SRA promotes hepatic steatosis through repressing the expression of adipose triglyceride lipase (ATGL)[J].Scientific Reports,2016,6:35531.
[44] KOECK E S,SEVILLA S,QURESHI F G,et al.Adipocyte exosomes induce transforming growth factor beta pathway dysregulation in hepatocytes:A novel paradigm for obesity-related liver disease[J].Journal of Surgical Research,2014,186(2):573.
[45] YI C,HAIXIU H,CHENGFU X,et al.Long non-coding RNA profiling in a non-alcoholic fatty liver disease rodent model:New insight into pathogenesis[J].International Journal of Molecular Sciences,2017,18(1):21.
[46] HUANG P,HUANG F Z,LIU H Z,et al.lncRNA MEG3 functions as a ceRNA in regulating hepatic lipogenesis by competitively binding to miR-21 with LRP6[J].Metabolism,2019,94:1-8.