肝癌外泌体miRNAs研究进展
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摘要
原发性肝癌是世界上最常见的恶性肿瘤之一,肝细胞癌(HCC)早期缺乏典型症状,一般不易诊断,超过80%的HCC患者在就诊时已处于中晚期。目前仍缺乏早期诊断HCC的生物标志物,且常规治疗方式效果不尽理想。因此,早期HCC的诊断迫切需要有效的、无创的、特异的生物标志物。此外,还需更多的治疗HCC的生物疗法。越来越多的外泌体miRNAs研究为HCC诊治提出了新的方向,其与HCC的发生、发展密切相关,在HCC诊治及预后评估等方面发挥着重要作用。因此,对HCC的诊治具有巨大的潜在价值。
Primary hepatic carcinoma is one of the most common malignant tumor,but the hepatocellular carcinoma(HCC)is lack of typical symptom in early stage,and the diagnosis is difficult,so more than 80% patients with HCC are in middle and advanced stage when diagnosis.Biomarkers for early diagnosis of HCC are still lacking,and more biological therapy for HCC is needed.The researches of exocrine miRNAs propose new direction for HCC treatment,the occurrence and development of HCC are closely related with miRNAs,which play an important role in diagnosis and prognosis of HCC,with enormous potential value.
Primary hepatic carcinoma is one of the most common malignant tumor,but the hepatocellular carcinoma(HCC)is lack of typical symptom in early stage,and the diagnosis is difficult,so more than 80% patients with HCC are in middle and advanced stage when diagnosis.Biomarkers for early diagnosis of HCC are still lacking,and more biological therapy for HCC is needed.The researches of exocrine miRNAs propose new direction for HCC treatment,the occurrence and development of HCC are closely related with miRNAs,which play an important role in diagnosis and prognosis of HCC,with enormous potential value.
引文
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[4] RAPOSO G,STOORVOGEL W.Extracellular vesicles:exosomes,microvesicles,and friends[J].J Cell Biol,2013,200(4):373-383.
[5] HUANG J Y,ZHANG K,CHEN D Q,et al.MicroRNA-451:epithelial-mesenchymal transition inhibitor and prognostic biomarker of hepatocelluar carcinoma[J].Oncotarget,2015,6(21):18613-18630.
[6] LI S,YAO J,XIE M,et al.Exosomal miRNAs in hepatocellular carcinoma development and clinical responses[J].J Hematol Oncol,2018,11(1):54.
[7] 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.
[8] TANG J,LI Y,LIU K,et al.Exosomal miR-9-3p suppresses HBGF-5expression and is a functional biomarker in hepatocellular carcinoma[J].Minerva Med,2018,109(1):15-23.
[9] ZHANG Z,LI X,SUN W,et al.Loss of exosomal miR-320afrom cancer-associated fibroblasts contributes to HCC proliferation and metastasis[J].Cancer Lett,2017,397:33-42.
[10]AUCHER A,RUDNICKA D,DAVIS D M.MicroRNAs transfer from human macrophages to hepato-carcinoma cells and inhibit proliferation[J].J Immunol,2013,191(12):6250-6260.
[11]KOGURE T,LIN W L,YAN I K,et al.Intercellular Nanovesicle-Mediated microRNA transfer:a mechanism of environmental modulation of hepatocellular cancer cell growth[J].Hepatology,2011,54(4):1237-1248.
[12]WANG F,LI L,PIONTEK K,et al.Exosome miR-335as a novel therapeutic strategy in hepatocellular carcinoma[J].Hepatology,2018,67(3):940-954.
[13]HE M,QIN H,POON T C,et al.Hepatocellular carcinoma-derived exosomes promote motility of immortalized hepatocyte through transfer of oncogenic proteins and RNAs[J].Carcinogenesis,2015,36(9):1008-1018.
[14]XIONG L,ZHEN S,YU Q,et al.HCV-E2inhibits hepatocellular carcinoma metastasis by stimulating mast cells to secrete exosomal shuttle microRNAs[J].Oncol Lett,2017,14(2):2141-2146.
[15]FANG T,LV H,LV G,et al.Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast activation to foster lung metastasis of liver cancer[J].Nat Commun,2018,9(1):191.
[16]TURLEY S J C V,ASTARITA J L.Immunological hallmarks of stromal cells in the tumour microenvironment[J].Nat Rev Immunol,2015,15(11):669-682.
[17]CHEN C,LUO F,LIU X L,et al.NF-kappa B-regulated exosomal miR-155promotes the inflammation associated with arsenite carcinogenesis[J].Cancer Lett,2017,388:21-33.
[18]GASCARD P,TLSTY T D.Carcinoma-associated fibroblasts:orchestrating the composition of malignancy[J].Genes Dev,2016,30(9):1002-1019.
[19]QU Z,WU J,WU J,et al.Exosomal miR-665as a novel minimally invasive biomarker for hepatocellular carcinoma diagnosis and prognosis[J].Oncotarget,2017,8(46):80666-80678.
[20]WANG H,HOU L,LI A,et al.Expression of serum exosomal microRNA-21in human hepatocellular carcinoma[J].Biomed Res Int,2014,2014:864894.
[21]SOHN W,KIM J,KANG S H,et al.Serum exosomal microRNAs as novel biomarkers for hepatocellular carcinoma[J].Exp Mol Med,2015,47:e184.
[22]SHI M,JIANG Y,YANG L,et al.Decreased levels of serum exosomal miR-638predict poor prognosis in hepatocellular carcinoma[J].J Cell Biochem,2018,119(6):4711-4716.
[23]SUGIMACHI K,MATSUMURA T,HIRATA H,et al.Identification of a bona fide microRNA biomarker in serum exosomes that predicts hepatocellular carcinoma recurrence after liver transplantation[J].Br J Cancer,2015,112(3):532-538.
[24]LIU W,HU J,ZHOU K,et al.Serum exosomal miR-125b is a novel prognostic marker for hepatocellular carcinoma[J].Onco Targets Ther,2017,10:3843-3851.
[25]YEO R W,LAI R C,ZHANG B,et al.Mesenchymal stem cell:an efficient mass producer of exosomes for drug delivery[J].Adv Drug Deliv Rev,2013,65(3):336-341.
[26]TSAI W C,HSU S D,HSU C S,et al.MicroRNA-122plays a critical role in liver homeostasis and hepatocarcinogenesis[J].J Clin Invest,2012,122(8):2884-2897.
[27]LOU G,SONG X,YANG FA,et al.Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma[J].J Hematol Oncol,2015,8:122.
[28]MITTELBRUNN M,GUTIERREZ-VAZQUEZ C,VILLARROYA-BELTRI C,et al.Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells[J].Nat Commun,2011,2:282.
[29]OKOYE I S,COOMES S M,PELLY V S,et al.MicroRNA-containing T-regulatory-cell-derived exosomes suppress pathogenic T helper 1cells[J].Immunity,2014,41(1):89-103.
[30]ALVAREZ-ERVITI L,SEOW Y,YIN H,et al.Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes[J].Nat Biotechnol,2011,29(4):341-345.
[31]WEI J X,LV L H,WAN Y L,et al.Vps4Afunctions as a tumor suppressor by regulating the secretion and uptake of exosomal MicroRNAs in human hepatoma cells[J].Hepatology,2015,61(4):1284-1294.