尿液中miRNA作为常见恶性肿瘤生物标志物研究进展

doi:10.3969/j.issn.1673-8640.2023.01.020

检验医学 ›› 2023, Vol. 38 ›› Issue (1): 94-99.DOI: 10.3969/j.issn.1673-8640.2023.01.020

尿液中miRNA作为常见恶性肿瘤生物标志物研究进展

吴亚婷¹, 李卓林¹, 雷艳², 贾如雪综述¹, 张胜行², 王水良审校¹()

1.厦门大学附属东方医院福建省适配体技术重点实验室，福建福州 350025
2.福建医科大学福总临床医学院中国人民解放军联勤保障部队第九〇〇医院检验科，福建福州 350025

收稿日期:2021-08-09 修回日期:2022-04-09 出版日期:2023-01-30 发布日期:2023-03-15
通讯作者: 王水良，E-mail：shuiliang.wang@xmu.edu.cn。
作者简介:吴亚婷，女，1990年生，学士，主要从事乳腺癌转移分子机制研究。
基金资助:
国家自然科学基金面上项目(81772848);福建省科技创新联合资金效用项目(2017Y9127);中国人民解放军联勤保障部队第九〇〇医院院立课题重点项目(2021ZD05)

Research progress of miRNA in urine as a biomarker for common malignant tumors

WU Yating¹, LI Zhuolin¹, LEI Yan², JIA Ruxue¹, ZHANG Shenghang², WANG Shuiliang¹()

1. Fujian Key Laboratory of Aptamers Technology，Dongfang Hospital，Xiamen University，Fuzhou 350025，Fujian，China
2. Department of Clinical Laboratory，Fuzhou General Clinical Medical School，the 900th Hospital of Chinese People's Liberation Army Joint Logistic Support Force，Fujian Medical University，Fuzhou 350025，Fujian，China

Received:2021-08-09 Revised:2022-04-09 Online:2023-01-30 Published:2023-03-15

摘要/Abstract

摘要：

目前，绝大部分中晚期恶性肿瘤患者的综合治疗效果仍然不尽如人意，因此肿瘤的早期诊断至关重要。微小RNA（miRNA）是一类广泛存在且生物学功能多样的非编码小分子RNA，越来越多的研究发现因遗传或表观遗传学改变所致的特定miRNA的表达失调在恶性肿瘤进展过程中起着重要的致癌或促癌作用。miRNA可稳定存在于血液、尿液、脑脊液、唾液等生物体液或分泌物中。与血液等样本相比，尿液样本的液体活检具有易于处理和无创取样等优势，尿液miRNA作为潜在的新型肿瘤分子标志物也引起了临床越来越多的关注。文章就近年来尿液miRNA在临床常见恶性肿瘤患者中的研究进展进行综述，并对其未来可能的临床实际应用进行初步展望，提出亟待解决的问题，以期为相关研究提供参考。

关键词: 微小RNA, 恶性肿瘤, 生物标志物, 尿液

Abstract:

The comprehensive treatment effect of the majority of patients with advanced cancers is still desirable，so the early diagnosis of cancers is important. MicroRNAs（miRNA）are a class of non-coding small RNAs that exist widely and have various biological functions. More and more studies have shown that the dysregulated expression of specific miRNA caused by genetic or epigenetic changes plays a role in carcinogenesis，malignant progression. In view of the fact that miRNA can stably exist in blood，urine，cerebrospinal fluid，saliva and other biological fluids or secretions. Compared with blood and other fluid-based biopsies，urine-based biopsies have the advantages of easy handling and non-invasive sampling，so the research of urinary miRNA as a potential new tumor molecular marker has attracted more and more attention. This review summarizes the research progress of urinary miRNA as a non-invasive biomarker in the recent years. It makes a preliminary prospect for its possible clinical application in the future，and puts forward some urgent problems to be solved，so as to provide useful enlightenment for future related research.

Key words: MicroRNA, Malignant tumor, Biomarker, Urine

中图分类号:

R393

吴亚婷, 李卓林, 雷艳, 贾如雪, 张胜行, 王水良. 尿液中miRNA作为常见恶性肿瘤生物标志物研究进展[J]. 检验医学, 2023, 38(1): 94-99.

WU Yating, LI Zhuolin, LEI Yan, JIA Ruxue, ZHANG Shenghang, WANG Shuiliang. Research progress of miRNA in urine as a biomarker for common malignant tumors[J]. Laboratory Medicine, 2023, 38(1): 94-99.

图/表 1

参考文献 35

[1]	SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3):209-249. DOI URL
[2]	MALL C, ROCKE D M, DURBIN-JOHNSON B, et al. Stability of miRNA in human urine supports its biomarker potential[J]. Biomark Med, 2013, 7(4):623-631. DOI PMID
[3]	WANG C, DING M, ZHU Y Y, et al. Circulating miR-200a is a novel molecular biomarker for early-stage renal cell carcinoma[J]. ExRNA, 2019, 1:25. DOI
[4]	NAKADA C, TSUKAMOTO Y, MATSUURA K, et al. Overexpression of miR-210,a downstream target of HIF1α,causes centrosome amplification in renal carcinoma cells[J]. J Pathol, 2011, 224(2):280-288. DOI URL
[5]	PETROZZA V, COSTANTINI M, TITO C, et al. Emerging role of secreted miR-210-3p as potential biomarker for clear cell renal cell carcinoma metastasis[J]. Cancer Biomark, 2020, 27(2):181-188. DOI PMID
[6]	TANG C, WU Y, WANG X, et al. LncRNA MAFG-AS1 regulates miR-125b-5p/SphK1 axis to promote the proliferation,migration,and invasion of bladder cancer cells[J]. Hum Cell, 2021, 34(2):588-597. DOI
[7]	ERDMANN K, SALOMO K, KLIMOVA A, et al. Urinary microRNAs as potential markers for non-invasive diagnosis of bladder cancer[J]. Int J Mol Sci, 2020, 21(11):3814. DOI URL
[8]	陆阳, 梁伟, 宋永胜. 尿液miRNA143和miRNA133a在膀胱癌诊断中的应用[J]. 检验医学, 2018, 33(10):924-927.
[9]	FERLAY J, COLOMBET M, SOERJOMATARAM I, et al. Cancer statistics for the year 2020:an overview[J]. Int J Cancer, 2021.
[10]	PAIVA R M, ZAULI D A G, NETO B S, et al. Urinary microRNAs expression in prostate cancer diagnosis:a systematic review[J]. Clin Transl Oncol, 2020, 22(11):2061-2073. DOI
[11]	HASANOĞLU S, GÖNCÜ B, YÜCESAN E, et al. Investigating differential miRNA expression profiling using serum and urine specimens for detecting potential biomarkers for early prostate cancer diagnosis[J]. Turk J Med Sci, 2021, 51(4):1764-1774. DOI PMID
[12]	OKATO A, GOTO Y, KUROZUMI A, et al. Direct regulation of LAMP1 by tumor-suppressive microRNA-320a in prostate cancer[J]. Int J Oncol, 2016, 49(1):111-122. DOI PMID
[13]	OKUDA Y, SHIMURA T, IWASAKI H, et al. Urinary microRNA biomarkers for detecting the presence of esophageal cancer[J]. Sci Rep, 2021, 11(1):8508. DOI PMID
[14]	KAO H W, PAN C Y, LAI C H, et al. Urine miR-21-5p as a potential non-invasive biomarker for gastric cancer[J]. Oncotarget, 2017, 8(34):56389-56397. DOI URL
[15]	IWASAKI H, SHIMURA T, YAMADA T, et al. A novel urinary microRNA biomarker panel for detecting gastric cancer[J]. J Gastroenterol, 2019, 54(12):1061-1069. DOI PMID
[16]	ZHANG Z, CHEN S, FAN M, et al. Helicobacter pylori induces gastric cancer via down-regulating miR-375 to inhibit dendritic cell maturation[J]. Helicobacter, 2021, 26(4):e12813.
[17]	HASEGAWA S, EGUCHI H, NAGANO H, et al. MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and stemness in pancreatic cancer[J]. Br J Cancer, 2014, 111(8):1572-1580. DOI
[18]	ISHIGE F, HOSHINO I, IWATATE Y, et al. MIR1246 in body fluids as a biomarker for pancreatic cancer[J]. Sci Rep, 2020, 10(1):8723. DOI PMID
[19]	ABDALLA M A, HAJ-AHMAD Y. Promising candidate urinary microRNA biomarkers for the early detection of hepatocellular carcinoma among high-risk hepatitis C virus egyptian patients[J]. J Cancer, 2012, 3:19-31. PMID
[20]	LIU K, WU X, ZANG X, et al. TRAF4 regulates migration,invasion,and epithelial-mesenchymal transition via PI3K/AKT signaling in hepatocellular carcinoma[J]. Oncol Res, 2017, 25(8):1329-1340. DOI URL
[21]	ERBES T, HIRSCHFELD M, RÜCKER G, et al. Feasibility of urinary microRNA detection in breast cancer patients and its potential as an innovative non-invasive biomarker[J]. BMC Cancer, 2015, 15:193. DOI PMID
[22]	KIA V, PARYAN M, MORTAZAVI Y, et al. Evaluation of exosomal miR-9 and miR-155 targeting PTEN and DUSP14 in highly metastatic breast cancer and their effect on low metastatic cells[J]. J Cell Biochem, 2019, 120(4):5666-5676. DOI PMID
[23]	BAUTISTA-SÁNCHEZ D, ARRIAGA-CANON C, PEDROZA-TORRES A, et al. The promising role of miR-21 as a cancer biomarker and its importance in RNA-based therapeutics[J]. Mol Ther Nucleic Acids, 2020, 20:409-420. DOI URL
[24]	WANG S, HUANG J, LYU H, et al. Functional cooperation of miR-125a,miR-125b,and miR-205 in entinostat-induced downregulation of erbB2/erbB3 and apoptosis in breast cancer cells[J]. Cell Death Dis, 2013, 4(3):e556. DOI
[25]	SADRI NAHAND J, SHOJAIE L, AKHLAGH S A, et al. Cell death pathways and viruses:role of microRNAs[J]. Mol Ther Nucleic Acids, 2021, 24:487-511. DOI URL
[26]	HIRSCHFELD M, RÜCKER G, WEIß D, et al. Urinary exosomal microRNAs as potential non-invasive biomarkers in breast cancer detection[J]. Mol Diagn Ther, 2020, 24(2):215-232. DOI PMID
[27]	WANG J, WANG S, ZHOU J, et al. MiR-424-5p regulates cell proliferation,migration and invasion by targeting doublecortin-like kinase 1 in basal-like breast cancer[J]. Biomed Pharmacother, 2018, 102:147-152. DOI URL
[28]	AFTAB M, POOJARY S S, SESHAN V, et al. Urine miRNA signature as a potential non-invasive diagnostic and prognostic biomarker in cervical cancer[J]. Sci Rep, 2021, 11(1):10323. DOI PMID
[29]	ZHOU J, GONG G, TAN H, et al. Urinary microRNA-30a-5p is a potential biomarker for ovarian serous adenocarcinoma[J]. Oncol Rep, 2015, 33(6):2915-2923. DOI PMID
[30]	DONKERS H, HIRSCHFELD M, WEIß D, et al. Detection of microRNA in urine to identify patients with endometrial cancer:a feasibility study[J]. Int J Gynecol Cancer, 2021, 31(6):868-874. DOI URL
[31]	AALAMI A H, ABDEAHAD H, MESGARI M, et al. MicroRNA-223 in gastrointestinal cancers:a systematic review and diagnostic meta-analysis[J]. Eur J Clin Invest, 2021, 51(2):e13448.
[32]	KITANO Y, AOKI K, OHKA F, et al. Urinary MicroRNA-based diagnostic model for central nervous system tumors using nanowire scaffolds[J]. ACS Appl Mater Interfaces, 2021, 13(15):17316-17329. DOI URL
[33]	LI J, WANG C, MENG Q, et al. MicroRNAs in urine as diagnostic biomarkers for multiple myeloma[J]. Int J Lab Hematol, 2021, 43(2):227-234. DOI PMID
[34]	LOURENÇO C, CONSTÂNCIO V, HENRIQUE R, et al. Urinary extracellular vesicles as potential biomarkers for urologic cancers:an overview of current methods and advances[J]. Cancers(Basel), 2021, 13(7):1529.
[35]	YASUI T, YANAGIDA T, ITO S, et al. Unveiling massive numbers of cancer-related urinary-microRNA candidates via nanowires[J]. Sci Adv, 2017, 3(12):e1701133. DOI URL

肿瘤类型	表达上调	表达下调	分子机制	诊断意义	参考文献
泌尿系统肿瘤
肾细胞癌		miR-200a	促肿瘤生长	明确	[3]
	miR-210-3p		影响染色体稳定性	未明确	[5]
膀胱癌	miR-183	miR-125b、miR-145和miR-221	促细胞增殖、侵袭和迁移	明确	[7]
		miR-143、miR-133a	促细胞增殖、侵袭和迁移	明确	[8]
前列腺癌	miR-21-5p、miR-141-3p、miR-375和miR-574-3p		促细胞增殖	明确	[10]
		miR-320a	促细胞侵袭和迁移	未明确	[11]
消化系统肿瘤
食管癌	miR-1273f、miR-619-5p、miR-150-3p、miR-4327和miR-3135b		促细胞增殖	明确	[13]
胃癌	miR-21-5p		促细胞增殖	未明确	[14]
	miR-6807-5p、miR-6856-5p		机制未明	明确	[15]
胰腺癌	miR-1246		调控细胞周期	明确	[18]
丙型肝炎后HCC	miR-618	miR-650	激活PI3K信号通路	明确	[19]
生殖系统肿瘤
乳腺癌	miR-155	miR-21、miR-125b和miR-451、	激活PI3K信号通路	明确	[21]
	miR-424	miR-423、miR-660和let7-i	调控细胞增殖、侵袭和迁移能力	明确	[27]
宫颈癌	miR-21-5p、miR-199-5p、miR-155-5p	miR-34a-5p、miR-145-5p、miR-218-5p	调控肿瘤细胞增殖、凋亡、迁移、侵袭和血管生成	明确	[28]
卵巢浆液性腺癌	miR-30a-5p		机制未明	明确	[29]
子宫内膜癌	miR-223		机制未明	未明确	[30]
其他肿瘤
多发性骨髓瘤		miR-134-5p、miR-6500-5p、miR-548q和miR-548y	机制未明	明确	[33]

肿瘤类型	表达上调	表达下调	分子机制	诊断意义	参考文献
泌尿系统肿瘤
肾细胞癌		miR-200a	促肿瘤生长	明确	[3]
	miR-210-3p		影响染色体稳定性	未明确	[5]
膀胱癌	miR-183	miR-125b、miR-145和miR-221	促细胞增殖、侵袭和迁移	明确	[7]
		miR-143、miR-133a	促细胞增殖、侵袭和迁移	明确	[8]
前列腺癌	miR-21-5p、miR-141-3p、miR-375和miR-574-3p		促细胞增殖	明确	[10]
		miR-320a	促细胞侵袭和迁移	未明确	[11]
消化系统肿瘤
食管癌	miR-1273f、miR-619-5p、miR-150-3p、miR-4327和miR-3135b		促细胞增殖	明确	[13]
胃癌	miR-21-5p		促细胞增殖	未明确	[14]
	miR-6807-5p、miR-6856-5p		机制未明	明确	[15]
胰腺癌	miR-1246		调控细胞周期	明确	[18]
丙型肝炎后HCC	miR-618	miR-650	激活PI3K信号通路	明确	[19]
生殖系统肿瘤
乳腺癌	miR-155	miR-21、miR-125b和miR-451、	激活PI3K信号通路	明确	[21]
	miR-424	miR-423、miR-660和let7-i	调控细胞增殖、侵袭和迁移能力	明确	[27]
宫颈癌	miR-21-5p、miR-199-5p、miR-155-5p	miR-34a-5p、miR-145-5p、miR-218-5p	调控肿瘤细胞增殖、凋亡、迁移、侵袭和血管生成	明确	[28]
卵巢浆液性腺癌	miR-30a-5p		机制未明	明确	[29]
子宫内膜癌	miR-223		机制未明	未明确	[30]
其他肿瘤
多发性骨髓瘤		miR-134-5p、miR-6500-5p、miR-548q和miR-548y	机制未明	明确	[33]

尿液中miRNA作为常见恶性肿瘤生物标志物研究进展

Research progress of miRNA in urine as a biomarker for common malignant tumors

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 1

参考文献 35

相关文章 15

编辑推荐

Metrics

[1]	王蓉, 邢连翔, 黄克亮, 李欣. miR-374靶向下调TRIM35表达可促进乳腺癌细胞增殖和侵袭[J]. 检验医学, 2023, 38(9): 812-817.
[2]	卫明珠, 潘继文, 罗锐, 陈俊辉. 凝血4项和肿瘤标志物对乙型肝炎相关肝癌的辅助诊断价值[J]. 检验医学, 2023, 38(9): 901-904.
[3]	孙泽朋, 王洪彬, 王建东, 宋德伟, 肖鹏. 心肌损伤多肽和蛋白类标志物方法学分析和进展[J]. 检验医学, 2023, 38(8): 784-789.
[4]	陈文举, 周勇, 徐佳佳, 王攀. 血清外泌体miR-23b-3p和miR-4429诊断HCC的价值[J]. 检验医学, 2023, 38(7): 624-628.
[5]	潘信, 吕颖, 李阳, 李荣国. miR-24-3p靶向CHD5影响甲状腺癌细胞迁移能力、侵袭能力和放射敏感性[J]. 检验医学, 2023, 38(7): 640-646.
[6]	王腾飞, 陈珊, 安和兵, 周蕾. 急性白血病患者外周血lncRNA CRNDE、miR-384表达及其临床意义[J]. 检验医学, 2023, 38(7): 686-691.
[7]	张莹, 景丽娟, 李丽. HBV携带者外周血单个核细胞miR-138表达与病毒增殖的关系[J]. 检验医学, 2023, 38(6): 559-562.
[8]	张敏, 王彬宇, 迟伟群, 刘禹. 外泌体非编码RNA作为疾病诊断生物标志物的研究进展[J]. 检验医学, 2023, 38(6): 594-598.
[9]	赵婧, 王佩, 卢丹丹, 齐丹丹, 李轩. 出血性脑卒中患者血清miR-4443、TRAF4相对表达量变化的临床意义[J]. 检验医学, 2023, 38(5): 413-418.
[10]	刘瑞丽, 李兰军, 贾旻蕾, 王一惠, 郝维纳. 胃癌组织miR-7-5p、NOVA2表达与患者临床预后的相关性[J]. 检验医学, 2023, 38(4): 325-329.
[11]	袁爽, 冯磊, 郭小芬, 付小玲, 许静, 刘弘扬. 子宫内膜癌组织miR-433的表达及其与化疗敏感性的关系[J]. 检验医学, 2023, 38(4): 337-341.
[12]	陈哲, 张灵, 刘洁, 王霞, 张斌, 高炳华. 血清miR-326与治疗相关性血液系统恶性肿瘤患者化疗敏感性和预后的关系[J]. 检验医学, 2023, 38(3): 251-256.
[13]	刘冲, 张静, 李胜, 赵奇. miR-335和Fra-1在乳腺癌中的表达及相互关系[J]. 检验医学, 2023, 38(2): 143-147.
[14]	刘庆阳, 袁建明, 夏进军, 姜风英, 王秋波, 王晓明. 基于GEO数据库和临床样本验证CXCL9作为类风湿关节炎生物标志物的研究[J]. 检验医学, 2023, 38(12): 1121-1129.
[15]	周福荣, 李龑杼, 刘勇敢. lncRNA SNP在结直肠癌易感性预测和预后评估中的应用[J]. 检验医学, 2023, 38(12): 1206-1210.