循环microRNA作为肝细胞癌标志物的研究现状

谢惠君; RashedNasot; 宁勇; 高川

doi:10.3969/j.issn.1001-5256.2021.02.042

循环microRNA作为肝细胞癌标志物的研究现状

DOI: 10.3969/j.issn.1001-5256.2021.02.042

湖北中医药大学检验学院，武汉 430065

基金项目:

湖北省“楚天学者计划”资助项目 (鄂教师函〔2016〕4号)

作者贡献声明：高川、宁勇负责课题设计；谢惠君、Rashed Nasot、高川撰写论文初稿；Rashed Nasot、宁勇参与收集数据和修改论文；宁勇指导撰写文章；高川、宁勇最后定稿。

详细信息

作者简介:
谢惠君(1996—)，女，主要从事临床检验诊断学方面的研究

通信作者:
高川，cgao@hbtcm.edu.cn

中图分类号: R735.7
计量
- 文章访问数: 413
- HTML全文浏览量: 164
- PDF下载量: 48
- 被引次数: 0
出版历程
- 收稿日期: 2020-11-06
- 录用日期: 2020-12-16
- 出版日期: 2021-02-20

Current status of research on circulating microRNAs as diagnostic markers for hepatocellular carcinoma

School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan 430065, China

摘要

摘要: 肝细胞癌(HCC)是最常见的原发性肝癌，其高死亡率与当前对HCC的诊断和监测手段不理想密切相关。microRNA(miRNA)在HCC的发生和进展过程中发挥重要作用，其异常表达是HCC病理中的常见现象，且miRNA能被细胞释放到循环血中稳定存在。通过讨论miRNA在HCC中作用的研究进展，提出循环miRNA有望成为HCC早期诊断、监测治疗和评估预后的潜在标志物，并分析了现阶段该潜在标志物在临床验证中所面临的问题。
- 癌, 肝细胞 /
- 微RNAs /
- 诊断
Abstract: Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and its high mortality rate is closely associated with the unsatisfactory diagnostic and monitoring methods for HCC at present. Some microRNAs (miRNAs) play an important role in the development and progression of HCC, and their abnormal expression is a common phenomenon in HCC pathology; in addition, miRNAs can be released into the circulating blood and remain stable in blood. By reviewing the research advances in the role of miRNAs in HCC, it is pointed out that miRNAs are expected to become potential markers for the early diagnosis, monitoring and treatment, and prognostic evaluation of HCC, and this article also analyzes related issues in the clinical verification of such potential markers.
- Carcinoma, Hepatocellular /
- MicroRNAs /
- Diagnosis

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参考文献(53)

[1]	SIEGEL RL, MILLER KD, JEMAL A. Cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(1): 7-30. DOI: 10.3322/caac.21590
[2]	LI X, GAO ZF, YAN J. Value of tumor markers in the diagnosis of early-stage primary liver cancer and related research advances[J/CD]. Electronic J Liver Tumor, 2014, 1(3): 41-45.(in Chinese) 李汛, 高增法, 严俊. 肿瘤标志物对早期原发性肝癌的诊断价值与研究进展[J/CD]. 肝癌电子杂志, 2014, 1(3): 41-45.
[3]	MCGLYNN KA, PETRICK JL, EL-SERAG HB. Epidemiology of hepatocellular carcinoma[J]. Hepatology, 2020.[Epub ahead of print]
[4]	HA M, KIM VN. Regulation of microRNA biogenesis[J]. Nat Rev Mol Cell Biol, 2014, 15(8): 509-524. DOI: 10.1038/nrm3838
[5]	KOZOMARA A, BIRGAOANU M, GRIFFITHS-JONES S. miRBase: From microRNA sequences to function[J]. Nucleic Acids Res, 2019, 47(D1): d155-d162. DOI: 10.1093/nar/gky1141
[6]	VICKERS KC, PALMISANO BT, SHOUCRI BM, et al. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins[J]. Nat Cell Biol, 2011, 13(4): 423-433. DOI: 10.1038/ncb2210
[7]	GEEKIYANAGE H, RAYATPISHEH S, WOHLSCHLEGEL JA, et al. Extracellular microRNAs in human circulation are associated with miRISC complexes that are accessible to anti-AGO2 antibody and can bind target mimic oligonucleotides[J]. Proc Natl Acad Sci U S A, 2020, 117(39): 24213-24223. DOI: 10.1073/pnas.2008323117
[8]	HAND NJ, MASTER ZR, LE LAY J, et al. Hepatic function is preserved in the absence of mature microRNAs[J]. Hepatology, 2009, 49(2): 618-626. DOI: 10.1002/hep.22656
[9]	SEKINE S, OGAWA R, ITO R, et al. Disruption of Dicer1 induces dysregulated fetal gene expression and promotes hepatocarcinogenesis[J]. Gastroenterology, 2009, 136(7): 2304-2315. DOI: 10.1053/j.gastro.2009.02.067
[10]	JIANG M, GONG X, XIAO XQ, et al. Expression of serum miRNA-122-3p in patients with CHB treated with PEG-interferon-alpha 2b[J]. Int J Virol, 2019, 26(5): 293-298.(in Chinese) DOI: 10.3760/cma.j.issn.1673-4092.2019.05.002 蒋敏, 龚兴, 肖新强, 等. 血清miRNA-122-3p在聚乙二醇干扰素-α2b治疗CHB患者中表达的研究[J]. 国际病毒学杂志, 2019, 26(5): 293-298. DOI: 10.3760/cma.j.issn.1673-4092.2019.05.002
[11]	BANDIERA S, PFEFFER S, BAUMERT TF, et al. miR-122-a key factor and therapeutic target in liver disease[J]. J Hepatol, 2015, 62(2): 448-457. DOI: 10.1016/j.jhep.2014.10.004
[12]	XUE X, ZHAO NY, YU HT, et al. Discovery of novel inhibitors disrupting HIF-1α/von Hippel-Lindau interaction through shape-based screening and cascade docking[J]. PeerJ, 2016, 4: e2757. DOI: 10.7717/peerj.2757
[13]	LI M, TANG Y, WU L, et al. The hepatocyte-specific HNF4α/miR-122 pathway contributes to iron overload-mediated hepatic inflammation[J]. Blood, 2017, 130(8): 1041-1051. DOI: 10.1182/blood-2016-12-755967
[14]	SHAN LQ, FANG Z, LIU H, et al.Mechanism of miR-92a in promoting proliferation and migration of hepatoma cells by down-regulating expression of RAB3B[J]. J Clin Exp Med, 2019, 18(12): 1266-1270.(in Chinese) DOI: 10.3969/j.issn.1671-4695.2019.12.010 单留群, 方征, 刘洪, 等. miR-92a通过下调RAB3B表达促进肝癌细胞增殖、迁移的机制分析[J]. 临床和实验医学杂志, 2019, 18(12): 1266-1270. DOI: 10.3969/j.issn.1671-4695.2019.12.010
[15]	MURAKAMI Y, YASUDA T, SAIGO K, et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues[J]. Oncogene, 2006, 25(17): 2537-2545. DOI: 10.1038/sj.onc.1209283
[16]	JIANG J, GUSEV Y, ADERCA I, et al. Association of microRNA expression in hepatocellular carcinomas with hepatitis infection, cirrhosis, and patient survival[J]. Clin Cancer Res, 2008, 14(2): 419-427. DOI: 10.1158/1078-0432.CCR-07-0523
[17]	PARK JK, KOGURE T, NUOVO GJ, et al. miR-221 silencing blocks hepatocellular carcinoma and promotes survival[J]. Cancer Res, 2011, 71(24): 7608-7616. DOI: 10.1158/0008-5472.CAN-11-1144
[18]	LI H, XIANG Z, LIU Y, et al. MicroRNA-133b inhibits proliferation, cellular migration, and invasion via targeting LASP1 in hepatocarcinoma cells[J]. Oncol Res, 2017, 25(8): 1269-1282. DOI: 10.3727/096504017X14850151453092
[19]	XIAN Y, WANG L, YAO B, et al. MicroRNA-769-5p contributes to the proliferation, migration and invasion of hepatocellular carcinoma cells by attenuating RYBP[J]. Biomed Pharmacother, 2019, 118: 109343. DOI: 10.1016/j.biopha.2019.109343
[20]	WU JY, LAI ZD, TIAN YF, et al. Expression and clinical significance of serum exosomal microRNA-221-3p in hepatocellular carcinoma[J]. J Clin Hepatol, 2020, 36(8): 1768-1772. (in Chinese) DOI: 10.3969/j.issn.1001-5256.2020.08.018 吴俊艺, 赖智德, 田毅峰, 等. 血清外泌体来源的microRNA-221-3p在肝细胞癌中的表达及意义[J]. 临床肝胆病杂志, 2020, 36(8): 1768-1772. DOI: 10.3969/j.issn.1001-5256.2020.08.018
[21]	WONG CC, AU SL, TSE AP, et al. Switching of pyruvate kinase isoform L to M2 promotes metabolic reprogramming in hepatocarcinogenesis[J]. PLoS One, 2014, 9(12): e115036. DOI: 10.1371/journal.pone.0115036
[22]	FORNARI F, GRAMANTIERI L, GIOVANNINI C, et al. MiR-122/cyclin G1 interaction modulates p53 activity and affects doxorubicin sensitivity of human hepatocarcinoma cells[J]. Cancer Res, 2009, 69(14): 5761-5767. DOI: 10.1158/0008-5472.CAN-08-4797
[23]	WANG SC, LIN XL, LI J, et al. MicroRNA-122 triggers mesenchymal-epithelial transition and suppresses hepatocellular carcinoma cell motility and invasion by targeting RhoA[J]. PLoS One, 2014, 9(7): e101330. DOI: 10.1371/journal.pone.0101330
[24]	GUO W, QIU Z, WANG Z, et al. MiR-199a-5p is negatively associated with malignancies and regulates glycolysis and lactate production by targeting hexokinase 2 in liver cancer[J]. Hepatology, 2015, 62(4): 1132-1144. DOI: 10.1002/hep.27929
[25]	ZHANG LF, LOU JT, LU MH, et al. Suppression of miR-199a maturation by HuR is crucial for hypoxia-induced glycolytic switch in hepatocellular carcinoma[J]. EMBO J, 2015, 34(21): 2671-2685. DOI: 10.15252/embj.201591803
[26]	FORNARI F, MILAZZO M, CHIECO P, et al. MiR-199a-3p regulates mTOR and c-Met to influence the doxorubicin sensitivity of human hepatocarcinoma cells[J]. Cancer Res, 2010, 70(12): 5184-5193. DOI: 10.1158/0008-5472.CAN-10-0145
[27]	HOU J, LIN L, ZHOU W, et al. Identification of miRNomes in human liver and hepatocellular carcinoma reveals miR-199a/b-3p as therapeutic target for hepatocellular carcinoma[J]. Cancer Cell, 2011, 19(2): 232-243. DOI: 10.1016/j.ccr.2011.01.001
[28]	LIU Z, LI W, PANG Y, et al. SF3B4 is regulated by microRNA-133b and promotes cell proliferation and metastasis in hepatocellular carcinoma[J]. EBioMedicine, 2018, 38: 57-68. DOI: 10.1016/j.ebiom.2018.10.067
[29]	FORNARI F, GRAMANTIERI L, FERRACIN M, et al. MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma[J]. Oncogene, 2008, 27(43): 5651-5661. DOI: 10.1038/onc.2008.178
[30]	PINEAU P, VOLINIA S, MCJUNKIN K, et al. miR-221 overexpression contributes to liver tumorigenesis[J]. Proc Natl Acad Sci U S A, 2010, 107(1): 264-269. DOI: 10.1073/pnas.0907904107
[31]	GRAMANTIERI L, FORNARI F, FERRACIN M, et al. MicroRNA-221 targets Bmf in hepatocellular carcinoma and correlates with tumor multifocality[J]. Clin Cancer Res, 2009, 15(16): 5073-5081. DOI: 10.1158/1078-0432.CCR-09-0092
[32]	FORNARI F, POLLUTRI D, PATRIZI C, et al. In hepatocellular carcinoma miR-221 modulates sorafenib resistance through inhibition of Caspase-3-mediated apoptosis[J]. Clin Cancer Res, 2017, 23(14): 3953-3965. DOI: 10.1158/1078-0432.CCR-16-1464
[33]	LI LM, HU ZB, ZHOU ZX, et al. Serum microRNA profiles serve as novel biomarkers for HBV infection and diagnosis of HBV-positive hepatocarcinoma[J]. Cancer Res, 2010, 70(23): 9798-9807. DOI: 10.1158/0008-5472.CAN-10-1001
[34]	ZHOU J, YU L, GAO X, et al. Plasma microRNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma[J]. J Clin Oncol, 2011, 29(36): 4781-4788. DOI: 10.1200/JCO.2011.38.2697
[35]	LIN XJ, CHONG Y, GUO ZW, et al. A serum microRNA classifier for early detection of hepatocellular carcinoma: A multicentre, retrospective, longitudinal biomarker identification study with a nested case-control study[J]. Lancet Oncol, 2015, 16(7): 804-815. DOI: 10.1016/S1470-2045(15)00048-0
[36]	EL-ABD NE, FAWZY NA, EL-SHEIKH SM, et al. Circulating miRNA-122, miRNA-199a, and miRNA-16 as biomarkers for early detection of hepatocellular carcinoma in egyptian patients with chronic hepatitis C virus infection[J]. Mol Diagn Ther, 2015, 19(4): 213-220. DOI: 10.1007/s40291-015-0148-1
[37]	NOMAIR AM, ISSA NM, MADKOUR MA, et al. The clinical significance of serum miRNA-224 expression in hepatocellular carcinoma[J]. Clin Exp Hepatol, 2020, 6(1): 20-27. DOI: 10.5114/ceh.2020.93052
[38]	de RIE D, ABUGESSAISA I, ALAM T, et al. An integrated expression atlas of miRNAs and their promoters in human and mouse[J]. Nat Biotechnol, 2017, 35(9): 872-878. DOI: 10.1038/nbt.3947
[39]	DA FONSECA B, DOMINGUES DS, PASCHOAL AR. mirtronDB: A mirtron knowledge base[J]. Bioinformatics, 2019, 35(19): 3873-3874. DOI: 10.1093/bioinformatics/btz153
[40]	LIU M, ROTH A, YU M, et al. The IGF2 intronic miR-483 selectively enhances transcription from IGF2 fetal promoters and enhances tumorigenesis[J]. Genes Dev, 2013, 27(23): 2543-2548. DOI: 10.1101/gad.224170.113
[41]	SHANG R, BAEK SC, KIM K, et al. Genomic clustering facilitates nuclear processing of suboptimal pri-miRNA loci[J]. Mol Cell, 2020, 78(2): 303-316. DOI: 10.1016/j.molcel.2020.02.009
[42]	CANTINI L, BERTOLI G, CAVA C, et al. Identification of microRNA clusters cooperatively acting on epithelial to mesenchymal transition in triple negative breast cancer[J]. Nucleic Acids Res, 2019, 47(5): 2205-2215. DOI: 10.1093/nar/gkz016
[43]	WU J, DONG T, CHEN T, et al. Hepatic exosome-derived miR-130a-3p attenuates glucose intolerance via suppressing PHLPP2 gene in adipocyte[J]. Metabolism, 2020, 103: 154006. DOI: 10.1016/j.metabol.2019.154006
[44]	DING J, XU Z, ZHANG Y, et al. Exosome-mediated miR-222 transferring: An insight into NF-κB-mediated breast cancer metastasis[J]. Exp Cell Res, 2018, 369(1): 129-138. DOI: 10.1016/j.yexcr.2018.05.014
[45]	WEBER JA, BAXTER DH, ZHANG S, et al. The microRNA spectrum in 12 body fluids[J]. Clin Chem, 2010, 56(11): 1733-1741. DOI: 10.1373/clinchem.2010.147405
[46]	HEEGAARD NH, SCHETTER AJ, WELSH JA, et al. Circulating micro-RNA expression profiles in early stage nonsmall cell lung cancer[J]. Int J Cancer, 2012, 130(6): 1378-1386. DOI: 10.1002/ijc.26153
[47]	HENEGHAN HM, MILLER N, LOWERY AJ, et al. Circulating microRNAs as novel minimally invasive biomarkers for breast cancer[J]. Ann Surg, 2010, 251(3): 499-505. DOI: 10.1097/SLA.0b013e3181cc939f
[48]	KROH EM, PARKIN RK, MITCHELL PS, et al. Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR)[J]. Methods, 2010, 50(4): 298-301. DOI: 10.1016/j.ymeth.2010.01.032
[49]	XU J, WU C, CHE X, et al. Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis[J]. Mol Carcinog, 2011, 50(2): 136-142. DOI: 10.1002/mc.20712
[50]	PELTIER HJ, LATHAM GJ. Normalization of microRNA expression levels in quantitative RT-PCR assays: Identification of suitable reference RNA targets in normal and cancerous human solid tissues[J]. RNA, 2008, 14(5): 844-852. DOI: 10.1261/rna.939908
[51]	WANG R, ZHU X, XING Y, et al. Multitag-regulated cascade reaction: A generalizable ultrasensitive microRNA biosensing approach for cancer prognosis[J]. ACS Appl Mater Interfaces, 2019, 11(40): 36444-36448. DOI: 10.1021/acsami.9b14452
[52]	QIU X, HILDEBRANDT N. Rapid and multiplexed microRNA diagnostic assay using quantum dot-based förster resonance energy transfer[J]. ACS Nano, 2015, 9(8): 8449-8457. DOI: 10.1021/acsnano.5b03364
[53]	GIRAY BG, EMEKDAS G, TEZCAN S, et al. Profiles of serum microRNAs; miR-125b-5p and miR223-3p serve as novel biomarkers for HBV-positive hepatocellular carcinoma[J]. Mol Biol Rep, 2014, 41(7): 4513-4519. DOI: 10.1007/s11033-014-3322-3