外泌体miRNA在胰腺癌研究中的进展

doi:10.3969/j.issn.1673-8640.2018.011.017

摘要/Abstract

摘要：

外泌体是直径为30~100 nm的囊泡样小体,能通过与靶细胞的细胞膜融合、胞吞作用等方式将其携带的微小RNA（miRNA）、蛋白质等传递至靶细胞中,介导细胞间的信息交流并调控细胞的生理功能。近年研究发现,外泌体miRNA在胰腺癌（PC）的发生、发展及诊断中具有重要作用,有望为PC的诊断和治疗提供新的思路。文章结合国内外研究现状,对外泌体miRNA在PC中的作用进行综述。

关键词: 胰腺癌, 外泌体, 微小RNA

Abstract:

Exosomes are sorts of small extracellular vesicles ranging approximately from 30 nm to 100 nm in diameter,which can serve as carriers transporting microRNA（miRNA）,protein and others to target cells by means of cell membrane fusion and cell swallowing,further mediating cell communication and regulating cell physiological function. In recent years,the related researches have found that exosomal miRNA plays a role in the occurrence,development and clinical diagnosis of pancreatic cancer（PC）,which is expected to provide new ideas for the diagnosis and treatment of PC. In this review,the role of exosomal miRNA in PC will be introduced based on domestic and overseas research status.

Key words: Pancreatic cancer, Exosome, MicroRNA

中图分类号:

R446.1

陈佳, 王健, 金炜, 陈旭东, 胡晓波. 外泌体miRNA在胰腺癌研究中的进展[J]. 检验医学, 2018, 33(11): 1049-1052.

CHEN Jia, WANG Jian, JIN Wei, CHEN Xudong, HU Xiaobo. Research progress of exosomal miRNA in pancreatic cancer[J]. Laboratory Medicine, 2018, 33(11): 1049-1052.

参考文献 36

[1]	SIEGEL R L,MILLER K D,JEMAL A.Cancer statistics,2017[J]. CA Cancer J Clin,2017,67(1):7-30.
[2]	KAMISAWA T,WOOD L D,ITOI T,et al.Pancreatic cancer[J]. Lancet,2016,388(10039):73-85.
[3]	ZHOU B,XU J W,CHENG Y G,et al.Early detection of pancreatic cancer:where are we now and where are we going?[J]. Int J Cancer,2017,141(2):231-241.
[4]	NATH S,MANDAL C,CHATTERJEE U,et al.Association of cytosolic sialidase Neu2 with plasma membrane enhances Fas-mediated apoptosis by impairing PI3K-Akt/m TOR-mediated pathway in pancreatic cancer cells[J]. Cell Death Dis,2018,9(2):210.
[5]	GOMEZ-RUBIO P,ZOCK J P,RAVA M,et al.Reduced risk of pancreatic cancer associated with asthma and nasal allergies[J]. Gut,2017,66(2):314-322.
[6]	ARMSTRONG E A,BEAL E W,CHAKEDIS J,et al.Exosomes in pancreatic cancer:from early detection to treatment[J]. J Gastrointest Surg,2018,22(4):737-750.
[7]	QIU J,YANG G,FENG M,et al.Extracellular vesicles as mediators of the progression and chemoresistance of pancreatic cancer and their potential clinical applications[J]. Mol Cancer,2018, 17(1):2.
[8]	ZHAO C,GAO F,WENG S,et al.Pancreatic cancer and associated exosomes[J]. Cancer Biomark,2017,20(4):357-367.
[9]	JIN H,WU Y,TAN X.The role of pancreatic cancer-derived exosomes in cancer progress and their potential application as biomarkers[J]. Clin Transl Oncol,2017,19(8):921-930.
[10]	PATEL G K,PATTON M C,SINGH S,et al.Pancreatic cancer exosomes:shedding off for a meaningful journey[J]. Pancreat Disord Ther,2016,6(2):e148.
[11]	ROBINSON S M,FAN L,WHITE S A,et al.The role of exosomes in the pathogenesis of pancreatic ductal adenocarcinoma[J]. Int J Biochem Cell Biol,2016,75:131-139.
[12]	SUN W,LUO J D,JIANG H,et al.Tumor exosomes:a double-edged sword in cancer therapy[J]. Acta Pharmacol Sin,2018,39(4):534-541.
[13]	ZAMANIAN M,FRASER L M,AGBEDANU P N,et al.Release of small RNA-containing exosome- like vesicles from the human filarial parasite brugia malayi[J]. PLoS Negl Trop Dis,2015,9(9):e0004069.
[14]	MILANE L,SINGH A,MATTHEOLABAKIS G,et al.Exosome mediated communication within the tumor microenvironment[J]. J Control Release,2015,219:278-294.
[15]	DE TORO J,HERSCHLIK L,WALDNER C,et al.Emerging roles of exosomes in normal and pathological conditions:new insights for diagnosis and therapeutic applications[J]. Front Immunol,2015,6:203.
[16]	SATO-KUWABARA Y,MELO S A,SOARES F A,et al.The fusion of two worlds:noncoding RNAs and extracellular vesicles-diagnostic and therapeutic implications(review)[J]. Int J Oncol,2015,46(1):17-27.
[17]	TKACH M,THÉRY C. Communication by extracellular vesicles:where we are and where we need to go[J]. Cell,2016,164(6):1226-1232.
[18]	CAI M,KOLLURU G K,AHMED A.Small molecule,big prospects:microRNA in pregnancy and its complications[J]. J Pregnancy,2017,2017:6972732.
[19]	AMERES S L,HORWICH M D,HUNG J H,et al.Target RNA-directed trimming and tailing of small silencing RNAs[J]. Science,2010,328(5985):1534-1539.
[20]	BIDARIMATH M,KHALAJ K,WESSELS J M,et al.MicroRNAs,immune cells and pregnancy[J]. Cell Mol Immunol,2014,11(6):538-547.
[21]	CATALANOTTO C,COGONI C,ZARDO G. MicroRNA in control of gene expression:an overview of nuclear functions[J]. Int J Mol Sci,2016,17(10):pii:E1712.
[22]	JONAS S,IZAURRALDE E.Towards a molecular understanding of microRNA-mediated gene silencing[J]. Nat Rev Genet,2015,16(7):421-433.
[23]	XIAO M,LI J,LI W,et al.MicroRNAs activate gene transcription epigenetically as an enhancer trigger[J]. RNA Biol,2017,14(10):1326-1334.
[24]	DING G,ZHOU L,QIAN Y,et al.Pancreatic cancer-derived exosomes transfer miRNAs to dendritic cells and inhibit RFXAP expression via miR-212-3p[J]. Oncotarget,2015,6(30):29877-29888.
[25]	ZHOU M,CHEN J,ZHOU L,et al.Pancreatic cancer derived exosomes regulate the expression of TLR4 in dendritic cells via miR-203[J]. Cell Immunol,2014,292(1-2):65-69.
[26]	TOMINAGA N,KOSAKA N,ONO M,et al.Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood-brain barrier[J]. Nat Commun,2015,6:6716.
[27]	LIU Y,LUO F,WANG B,et al.STAT3-regulated exosomal miR-21 promotes angiogenesis and is involved in neoplastic processes of transformed human bronchial epithelial cells[J]. Cancer Lett,2016,370(1):125-135.
[28]	ZHANG L,ZHANG S,YAO J,et al.Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth[J]. Nature,2015,527(7576):100-104.
[29]	BASU S,BHATTACHARYYA S N.Insulin-like growth factor-1 prevents miR-122 production in neighbouring cells to curtail its intercellular transfer to ensure proliferation of human hepatoma cells[J]. Nucleic Acids Res,2014,42(11):7170-7185.
[30]	CHEN D,WU X,XIA M,et al.Upregulated exosomic miR-23b-3p plays regulatory roles in the progression of pancreatic cancer[J]. Oncol Rep,2017,38(4):2182-2188.
[31]	TAKIKAWA T,MASAMUNE A,YOSHIDA N,et al.Exosomes derived from pancreatic stellate cells:microRNA signature and effects on pancreatic cancer cells[J]. Pancreas,2017,46(1):19-27.
[32]	MIKAMORI M,YAMADA D,EGUCHI H,et al.MicroRNA-155 controls exosome synthesis and promotes gemcitabine resistance in pancreatic ductal adenocarcinoma[J]. Sci Rep,2017,7:42339.
[33]	BORSOI C,LEONARD F,LEE Y,et al.Gemcitabine enhances the transport of nanovector-albumin-bound paclitaxel in gemcitabine-resistant pancreatic ductal adenocarcinoma[J]. Cancer Lett,2017,403:296-304.
[34]	QUE R,DING G,CHEN J,et al.Analysis of serum exosomal microRNAs and clinicopathologic features of patients with pancreatic adenocarcinoma[J]. World J Surg Oncol,2013,11:219.
[35]	MADHAVAN B,YUE S,GALLI U,et al.Combined evaluation of a panel of protein and miRNA serum-exosome biomarkers for pancreatic cancer diagnosis increases sensitivity and specificity[J]. Int J Cancer,2014,136(11):2616-2627.
[36]	MACHIDA T,TOMOFUJI T,MARUYAMA T,et al.miR-1246 and miR-4644 in salivary exosome as potential biomarkers for pancreatobiliary tract cancer[J]. Oncol Rep,2016,36(4):2375-2381.