lncRNA在女性生殖系统恶性肿瘤中的功能和作用机制
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摘要
长链非编码RNA(long non-coding RNA,lncRNA)是指长度超过200个核苷酸,无典型开放阅读框,且不能编码蛋白质的RNA转录本。lncRNA在机体的转录、翻译和RNA可变剪切等生命过程中发挥着重要的生理作用。lncRNA在机体中通过分子引导的方式或作为分子诱饵、分子信号及分子支架发挥其功能。近些年来,大量的研究表明,lncRNA的异常表达与女性生殖系统恶性肿瘤密切相关。基于国内外最新研究,本文主要总结了lncRNA在卵巢癌、宫颈癌和子宫内膜癌中的作用机制,简要介绍了lncRNA在绒毛膜癌、外阴癌等其他女性生殖系统恶性肿瘤中的作用。lncRNA通过各种机制在癌症进展中扮演着癌基因或抑癌基因的角色。随着研究方法和技术的发展,lncRNA作为可靠的生物标志和新的癌症治疗靶点的潜力也将得到进一步开发,从而为保障女性生殖健康提供新思路和新方法。
Long non-coding RNA(lncRNA) refers to an RNA transcript that is more than 200 nucleotides in length, has no typical open reading frame, and cannot encode a protein. It plays an important physiological role in biological processes such as transcription, translation, and RNA variability. It functions in the body by molecular guidance or as a molecular bait, molecular signal, and molecular scaffold. In recent years, a large number of studies have shown that lncRNA abnormal expression is closely related to female reproductive malignancies. Based on the latest research at home and abroad, we summarized the mechanisms of lncRNA in ovarian cancer, cervical cancer, and endometrial cancer, and briefly introduced the roles of lncRNA in other female reproductive malignancies such as endometrial cancer and vulvar cancer. It functions as an oncogene or tumor suppressor gene in cancer progression through various mechanisms. With the development of research methods and techniques, the potentials of lncRNA as a reliable biomarker and a new cancer therapeutic target will also be further developed, aiming to provide new ideas and methods to protect female reproductive health.
Long non-coding RNA(lncRNA) refers to an RNA transcript that is more than 200 nucleotides in length, has no typical open reading frame, and cannot encode a protein. It plays an important physiological role in biological processes such as transcription, translation, and RNA variability. It functions in the body by molecular guidance or as a molecular bait, molecular signal, and molecular scaffold. In recent years, a large number of studies have shown that lncRNA abnormal expression is closely related to female reproductive malignancies. Based on the latest research at home and abroad, we summarized the mechanisms of lncRNA in ovarian cancer, cervical cancer, and endometrial cancer, and briefly introduced the roles of lncRNA in other female reproductive malignancies such as endometrial cancer and vulvar cancer. It functions as an oncogene or tumor suppressor gene in cancer progression through various mechanisms. With the development of research methods and techniques, the potentials of lncRNA as a reliable biomarker and a new cancer therapeutic target will also be further developed, aiming to provide new ideas and methods to protect female reproductive health.
引文
[1]PONTING C P,OLIVER P L,REIK W.Evolution and functions of long noncoding RNAs[J].Cell,2009,136(4):629-641.
[2]MESEURE D,DRAK ALSIBAI K,NICOLAS A,et al.Long noncoding RNAs as new architects in cancer epigenetics,prognostic biomarkers,and potential therapeutic targets[J].Biomed Res Int,2015,2015:320214.
[3]XIAO Q,ZHENG F,TANG Q,et al.Repression of PDK1-and lncRNA HOTAIR-mediated EZH2 gene expression contributes to the enhancement of atractylenolide 1 and erlotinib in the inhibition of human lung cancer cells[J].Cell Physiol Biochem,2018,49(4):1615-1632.
[4]WU Q,GUO L,JIANG F,et al.Analysis of the miRNA-mRNA-lncRNA networks in ER+and ER-breast cancer cell lines[J].J Cell Mol Med,2015,19(12):2874-2887.
[5]LIU J,DING D,JIANG Z,et al.Long non-coding RNA CCAT1/miR-148a/PKCζprevents cell migration of prostate cancer by altering macrophage polarization[J].Prostate,2019,79(1):105-112.
[6]刘慧强.我国宫颈癌流行病学特征和高危因素分析[J].中国妇幼保健,2016,31(6):1258-1260.
[7]WEIDERPASS E,LABRECHE F.Malignant tumors of the female reproductive system[J].Saf Health Work,2012,3(3):166-180.
[8]QIU J J,LIN Y Y,YE L C,et al.Overexpression of long noncoding RNA HOTAIR predicts poor patient prognosis and promotes tumor metastasis in epithelial ovarian cancer[J].Gynecol Oncol,2014,134(1):121-128.
[9]QIU J J,WANG Y,DING J X,et al.The long non-coding RNAHOTAIR promotes the proliferation of serous ovarian cancer cells through the regulation of cell cycle arrest and apoptosis[J].Exp Cell Res,2015,333(2):238-248.
[10]WU H,SHANG X,SHI Y,et al.Genetic variants of lncRNAHOTAIR and risk of epithelial ovarian cancer among Chinese women[J].Oncotarget,2016,7(27):41047-41052.
[11]YIWEI T,HUA H,HUI G,et al.HOTAIR interacting with MAPK1regulates ovarian cancer skov3 cell proliferation,migration,and invasion[J].Med Sci Monit,2015,21:1856-1863.
[12]DONG L,HUI L.HOTAIR promotes proliferation,migration,and invasion of ovarian cancer SKOV3 cells through regulating PIK3R3[J].Med Sci Monit,2016,22:325-331.
[13]ZHANG Z,CHENG J,WU Y,et al.lncRNA HOTAIR controls the expression of Rab22a by sponging miR-373 in ovarian cancer[J].Mol Med Rep,2016,14(3):2465-2472.
[14]MENDOZA P,ORTIZ R,DIAZ J,et al.Rab5 activation promotes focal adhesion disassembly,migration and invasiveness in tumor cells[J].J Cell Sci,2013,126:3835-3847.
[15]WANG Y,WANG H,SONG T,et al.HOTAIR is a potential target for the treatment of cisplatin-resistant ovarian cancer[J].Mol Med Rep,2015,12(2):2211-2216.
[16]RUPAIMOOLE R,LEE J,HAEMMERLE M,et al.Long noncoding RNA ceruloplasmin promotes cancer growth by altering glycolysis[J].Cell Rep,2015,13(11):2395-2402.
[17]RANGEL L B,SHERMAN-BAUST C A,WERNYJ R P,et al.Characterization of novel human ovarian cancer-specific transcripts(HOSTs)identified by serial analysis of gene expression[J].Oncogene,2003,22(46):7225-7232.
[18]刘静,彭萍,汪先桃.上皮性卵巢癌中HOST2 lncRNA的表达及临床意义[J].中国医学创新,2015,12(3):34-36.
[19]GAO Y,MENG H,LIU S,et al.lncRNA-HOST2 regulates cell biological behaviors in epithelial ovarian cancer through a mechanism involving microRNA let-7b[J].Hum Mol Genet,2015,24(3):841-852.
[20]ZHENG Z G,XU H,SUO S S,et al.The essential role of H19contributing to cisplatin resistance by regulating glutathione metabolism in high-grade serous ovarian cancer[J].Sci Rep,2016,6:26093.
[21]YAN H,XIA J Y,FENG F Z.Long non-coding RNAENST00000457645 reverses cisplatin resistance in CP70ovarian cancer cells[J].Genet Mol Res,2017,16(1):gmr16019411.
[22]LI H,LIU C,LU Z,et al.Upregulation of the long non-coding RNA SPRY4-IT1 indicates a poor prognosis and promotes tumorigenesis in ovarian cancer[J].Biomed Pharmacother,2017,88:529-534.
[23]CHAI Y,LIU J,ZHANG Z,et al.HuR-regulated lncRNA NEAT1stability in tumorigenesis and progression of ovarian cancer[J].Cancer Med,2016,5(7):1588-1598.
[24]WU Y,DENG Y,ZHU J,et al.Long noncoding RNA NEAT1,regulated by LIN28B,promotes cell proliferation and migration through sponging miR-506 in high-grade serous ovarian cancer[J].Cell Death Dis,2018,9(9):861.
[25]WANG C,QI S,XIE C,et al.Upregulation of long non-coding RNA XIST has anticancer effects on epithelial ovarian cancer cells through inverse downregulation of hsa-miR-214-3p[J].J Gynecol Oncol,2018,29(6):e99.
[26]SHENG X,LI J,YANG L,et al.Promoter hypermethylation influences the suppressive role of maternally expressed 3,a long non-coding RNA,in the development of epithelial ovarian cancer[J].Oncol Rep,2014,32(1):277-285.
[27]KIM H J,LEE D W,YIM G W,et al.Long non-coding RNAHOTAIR is associated with human cervical cancer progression[J].Int J Oncol,2015,46(2):521-530.
[28]ZHENG P,XIONG Q,WU Y,et al.Quantitative proteomics analysis reveals novel insights into mechanisms of action of long noncoding RNA Hox transcript antisense intergenic RNA(HOTAIR)in heLa cells[J].Mol Cell Proteomics,2015,14(6):1447-1463.
[29]LI J,WANG Y,DONG R,et al.HOTAIR enhanced aggressive biological behaviors and induced radio-resistance via inhibiting p21 in cervical cancer[J].Tumour Biol,2015,36(5):3611-3619.
[30]SUN J,CHU H,JI J,et al.Long non-coding RNA HOTAIRmodulates HLA-G expression by absorbing miR-148a in human cervical cancer[J].Int J Oncol,2016,49(3):943-952.
[31]LIU M,JIA J,WANG X,et al.Long non-coding RNA HOTAIRpromotes cervical cancer progression through regulating BCL2 via targeting miR-143-3p[J].Cancer Biol Ther,2018,19(5):391-399.
[32]SHARMA S,MANDAL P,SADHUKHAN T,et al.Bridging links between long noncoding RNA HOTAIR and HPV oncoprotein E7 in cervical cancer pathogenesis[J].Sci Rep,2015,5:11724.
[33]HUANG C,YU Z,YANG H,et al.Increased MALAT1expression predicts poor prognosis in esophageal cancer patients[J].Biomed Pharmacother,2016,83:8-13.
[34]SUN R,QIN C,JIANG B,et al.Down-regulation of MALAT1inhibits cervical cancer cell invasion and metastasis by inhibition of epithelial-mesenchymal transition[J].Mol Biosyst,2016,12(3):952-962.
[35]赵晓宇,何政,欧阳玲.长链非编码RNA在妇科恶性肿瘤中的研究进展[J].现代肿瘤医学,2016,24(18):2993-2997.
[36]LU H,HE Y,LIN L,et al.Long non-coding RNA MALAT1modulates radiosensitivity of HR-HPV+cervical cancer via sponging miR-145[J].Tumour Biol,2016,37(2):1683-1691.
[37]LIU S,SONG L,ZENG S,et al.MALAT1-miR-124-RBG2 axis is involved in growth and invasion of HR-HPV-positive cervical cancer cells[J].Tumour Biol,2016,37(1):633-640.
[38]YANG M,ZHAI X,XIA B,et al.Long noncoding RNA CCHE1promotes cervical cancer cell proliferation via upregulating PCNA[J].Tumour Biol,2015,36(10):7615-7622.
[39]ZHANG J,YAO T,WANG Y,et al.Long noncoding RNAMEG3 is downregulated in cervical cancer and affects cell proliferation and apoptosis by regulating miR-21[J].Cancer Biol Ther,2016,17(1):104-113.
[40]ZHAO Y,YANG Y,TROVIK J,et al.A novel wnt regulatory axis in endometrioid endometrial cancer[J].Cancer Res,2014,74(18):5103-5117.
[41]LI Q,ZHANG C,CHEN R,et al.Disrupting MALAT1/miR-200c sponge decreases invasion and migration in endometrioid endometrial carcinoma[J].Cancer Lett,2016,383(1):28-40.
[42]GUO C,SONG W Q,SUN P,et al.lncRNA-GAS5 induces PTEN expression through inhibiting miR-103 in endometrial cancer cells[J].J Biomed Sci,2015,22:100.
[43]孙逊.188Re在肿瘤治疗中的应用[J].国外医学·放射医学核医学分册,2003,27(4):151-153.
[44]ZHAI W,LI X,WU S,et al.Microarray expression profile of lncRNAs and the upregulated ASLNC04080 lncRNA in human endometrial carcinoma[J].Int J Oncol,2015,46(5):2125-2137.
[45]赵燕凌,陈跃.188Re标记放射性药物研究进展[J].医学综述,2006,12(14):879-882.
[46]WANG Y,XUE K,GUAN Y,et al.Long noncoding RNALINC00261 suppresses cell proliferation and invasion and promotes cell apoptosis in human choriocarcinoma[J].Oncol Res,2017,25(5):733-742.
[47]SHI D,ZHANG Y,LU R,et al.The long non-coding RNA MALAT1 interacted with miR-218 modulates choriocarcinoma growth by targeting Fbxw8[J].Biomed Pharmacother,2018,97:543-550.
[48]MUYS B R,LORENZI J C,ZANETTE D L,et al.Placentaenriched LincRNAs MIR503HG and LINC00629 decrease migration and invasion potential of JEG-3 cell line[J].PLoSOne,2016,11(3):e0151560.
[49]NI S,ZHAO X,OUYANG L.Long non-coding RNA expression profile in vulvar squamous cell carcinoma and its clinical significance[J].Oncol Rep,2016,36(5):2571-2578.
[50]ZHOU J,YANG L,ZHONG T,et al.H19 lncRNA alters DNAmethylation genome wide by regulating S-adenosylhomocysteine hydrolase[J].Nat Commun,2015,6:10221.
[51]JOH R I,PALMIERI C M,HILL I T,et al.Regulation of histone methylation by noncoding RNAs[J].Biochim Biophys Acta,2014,1839(12):1385-1394.
[2]MESEURE D,DRAK ALSIBAI K,NICOLAS A,et al.Long noncoding RNAs as new architects in cancer epigenetics,prognostic biomarkers,and potential therapeutic targets[J].Biomed Res Int,2015,2015:320214.
[3]XIAO Q,ZHENG F,TANG Q,et al.Repression of PDK1-and lncRNA HOTAIR-mediated EZH2 gene expression contributes to the enhancement of atractylenolide 1 and erlotinib in the inhibition of human lung cancer cells[J].Cell Physiol Biochem,2018,49(4):1615-1632.
[4]WU Q,GUO L,JIANG F,et al.Analysis of the miRNA-mRNA-lncRNA networks in ER+and ER-breast cancer cell lines[J].J Cell Mol Med,2015,19(12):2874-2887.
[5]LIU J,DING D,JIANG Z,et al.Long non-coding RNA CCAT1/miR-148a/PKCζprevents cell migration of prostate cancer by altering macrophage polarization[J].Prostate,2019,79(1):105-112.
[6]刘慧强.我国宫颈癌流行病学特征和高危因素分析[J].中国妇幼保健,2016,31(6):1258-1260.
[7]WEIDERPASS E,LABRECHE F.Malignant tumors of the female reproductive system[J].Saf Health Work,2012,3(3):166-180.
[8]QIU J J,LIN Y Y,YE L C,et al.Overexpression of long noncoding RNA HOTAIR predicts poor patient prognosis and promotes tumor metastasis in epithelial ovarian cancer[J].Gynecol Oncol,2014,134(1):121-128.
[9]QIU J J,WANG Y,DING J X,et al.The long non-coding RNAHOTAIR promotes the proliferation of serous ovarian cancer cells through the regulation of cell cycle arrest and apoptosis[J].Exp Cell Res,2015,333(2):238-248.
[10]WU H,SHANG X,SHI Y,et al.Genetic variants of lncRNAHOTAIR and risk of epithelial ovarian cancer among Chinese women[J].Oncotarget,2016,7(27):41047-41052.
[11]YIWEI T,HUA H,HUI G,et al.HOTAIR interacting with MAPK1regulates ovarian cancer skov3 cell proliferation,migration,and invasion[J].Med Sci Monit,2015,21:1856-1863.
[12]DONG L,HUI L.HOTAIR promotes proliferation,migration,and invasion of ovarian cancer SKOV3 cells through regulating PIK3R3[J].Med Sci Monit,2016,22:325-331.
[13]ZHANG Z,CHENG J,WU Y,et al.lncRNA HOTAIR controls the expression of Rab22a by sponging miR-373 in ovarian cancer[J].Mol Med Rep,2016,14(3):2465-2472.
[14]MENDOZA P,ORTIZ R,DIAZ J,et al.Rab5 activation promotes focal adhesion disassembly,migration and invasiveness in tumor cells[J].J Cell Sci,2013,126:3835-3847.
[15]WANG Y,WANG H,SONG T,et al.HOTAIR is a potential target for the treatment of cisplatin-resistant ovarian cancer[J].Mol Med Rep,2015,12(2):2211-2216.
[16]RUPAIMOOLE R,LEE J,HAEMMERLE M,et al.Long noncoding RNA ceruloplasmin promotes cancer growth by altering glycolysis[J].Cell Rep,2015,13(11):2395-2402.
[17]RANGEL L B,SHERMAN-BAUST C A,WERNYJ R P,et al.Characterization of novel human ovarian cancer-specific transcripts(HOSTs)identified by serial analysis of gene expression[J].Oncogene,2003,22(46):7225-7232.
[18]刘静,彭萍,汪先桃.上皮性卵巢癌中HOST2 lncRNA的表达及临床意义[J].中国医学创新,2015,12(3):34-36.
[19]GAO Y,MENG H,LIU S,et al.lncRNA-HOST2 regulates cell biological behaviors in epithelial ovarian cancer through a mechanism involving microRNA let-7b[J].Hum Mol Genet,2015,24(3):841-852.
[20]ZHENG Z G,XU H,SUO S S,et al.The essential role of H19contributing to cisplatin resistance by regulating glutathione metabolism in high-grade serous ovarian cancer[J].Sci Rep,2016,6:26093.
[21]YAN H,XIA J Y,FENG F Z.Long non-coding RNAENST00000457645 reverses cisplatin resistance in CP70ovarian cancer cells[J].Genet Mol Res,2017,16(1):gmr16019411.
[22]LI H,LIU C,LU Z,et al.Upregulation of the long non-coding RNA SPRY4-IT1 indicates a poor prognosis and promotes tumorigenesis in ovarian cancer[J].Biomed Pharmacother,2017,88:529-534.
[23]CHAI Y,LIU J,ZHANG Z,et al.HuR-regulated lncRNA NEAT1stability in tumorigenesis and progression of ovarian cancer[J].Cancer Med,2016,5(7):1588-1598.
[24]WU Y,DENG Y,ZHU J,et al.Long noncoding RNA NEAT1,regulated by LIN28B,promotes cell proliferation and migration through sponging miR-506 in high-grade serous ovarian cancer[J].Cell Death Dis,2018,9(9):861.
[25]WANG C,QI S,XIE C,et al.Upregulation of long non-coding RNA XIST has anticancer effects on epithelial ovarian cancer cells through inverse downregulation of hsa-miR-214-3p[J].J Gynecol Oncol,2018,29(6):e99.
[26]SHENG X,LI J,YANG L,et al.Promoter hypermethylation influences the suppressive role of maternally expressed 3,a long non-coding RNA,in the development of epithelial ovarian cancer[J].Oncol Rep,2014,32(1):277-285.
[27]KIM H J,LEE D W,YIM G W,et al.Long non-coding RNAHOTAIR is associated with human cervical cancer progression[J].Int J Oncol,2015,46(2):521-530.
[28]ZHENG P,XIONG Q,WU Y,et al.Quantitative proteomics analysis reveals novel insights into mechanisms of action of long noncoding RNA Hox transcript antisense intergenic RNA(HOTAIR)in heLa cells[J].Mol Cell Proteomics,2015,14(6):1447-1463.
[29]LI J,WANG Y,DONG R,et al.HOTAIR enhanced aggressive biological behaviors and induced radio-resistance via inhibiting p21 in cervical cancer[J].Tumour Biol,2015,36(5):3611-3619.
[30]SUN J,CHU H,JI J,et al.Long non-coding RNA HOTAIRmodulates HLA-G expression by absorbing miR-148a in human cervical cancer[J].Int J Oncol,2016,49(3):943-952.
[31]LIU M,JIA J,WANG X,et al.Long non-coding RNA HOTAIRpromotes cervical cancer progression through regulating BCL2 via targeting miR-143-3p[J].Cancer Biol Ther,2018,19(5):391-399.
[32]SHARMA S,MANDAL P,SADHUKHAN T,et al.Bridging links between long noncoding RNA HOTAIR and HPV oncoprotein E7 in cervical cancer pathogenesis[J].Sci Rep,2015,5:11724.
[33]HUANG C,YU Z,YANG H,et al.Increased MALAT1expression predicts poor prognosis in esophageal cancer patients[J].Biomed Pharmacother,2016,83:8-13.
[34]SUN R,QIN C,JIANG B,et al.Down-regulation of MALAT1inhibits cervical cancer cell invasion and metastasis by inhibition of epithelial-mesenchymal transition[J].Mol Biosyst,2016,12(3):952-962.
[35]赵晓宇,何政,欧阳玲.长链非编码RNA在妇科恶性肿瘤中的研究进展[J].现代肿瘤医学,2016,24(18):2993-2997.
[36]LU H,HE Y,LIN L,et al.Long non-coding RNA MALAT1modulates radiosensitivity of HR-HPV+cervical cancer via sponging miR-145[J].Tumour Biol,2016,37(2):1683-1691.
[37]LIU S,SONG L,ZENG S,et al.MALAT1-miR-124-RBG2 axis is involved in growth and invasion of HR-HPV-positive cervical cancer cells[J].Tumour Biol,2016,37(1):633-640.
[38]YANG M,ZHAI X,XIA B,et al.Long noncoding RNA CCHE1promotes cervical cancer cell proliferation via upregulating PCNA[J].Tumour Biol,2015,36(10):7615-7622.
[39]ZHANG J,YAO T,WANG Y,et al.Long noncoding RNAMEG3 is downregulated in cervical cancer and affects cell proliferation and apoptosis by regulating miR-21[J].Cancer Biol Ther,2016,17(1):104-113.
[40]ZHAO Y,YANG Y,TROVIK J,et al.A novel wnt regulatory axis in endometrioid endometrial cancer[J].Cancer Res,2014,74(18):5103-5117.
[41]LI Q,ZHANG C,CHEN R,et al.Disrupting MALAT1/miR-200c sponge decreases invasion and migration in endometrioid endometrial carcinoma[J].Cancer Lett,2016,383(1):28-40.
[42]GUO C,SONG W Q,SUN P,et al.lncRNA-GAS5 induces PTEN expression through inhibiting miR-103 in endometrial cancer cells[J].J Biomed Sci,2015,22:100.
[43]孙逊.188Re在肿瘤治疗中的应用[J].国外医学·放射医学核医学分册,2003,27(4):151-153.
[44]ZHAI W,LI X,WU S,et al.Microarray expression profile of lncRNAs and the upregulated ASLNC04080 lncRNA in human endometrial carcinoma[J].Int J Oncol,2015,46(5):2125-2137.
[45]赵燕凌,陈跃.188Re标记放射性药物研究进展[J].医学综述,2006,12(14):879-882.
[46]WANG Y,XUE K,GUAN Y,et al.Long noncoding RNALINC00261 suppresses cell proliferation and invasion and promotes cell apoptosis in human choriocarcinoma[J].Oncol Res,2017,25(5):733-742.
[47]SHI D,ZHANG Y,LU R,et al.The long non-coding RNA MALAT1 interacted with miR-218 modulates choriocarcinoma growth by targeting Fbxw8[J].Biomed Pharmacother,2018,97:543-550.
[48]MUYS B R,LORENZI J C,ZANETTE D L,et al.Placentaenriched LincRNAs MIR503HG and LINC00629 decrease migration and invasion potential of JEG-3 cell line[J].PLoSOne,2016,11(3):e0151560.
[49]NI S,ZHAO X,OUYANG L.Long non-coding RNA expression profile in vulvar squamous cell carcinoma and its clinical significance[J].Oncol Rep,2016,36(5):2571-2578.
[50]ZHOU J,YANG L,ZHONG T,et al.H19 lncRNA alters DNAmethylation genome wide by regulating S-adenosylhomocysteine hydrolase[J].Nat Commun,2015,6:10221.
[51]JOH R I,PALMIERI C M,HILL I T,et al.Regulation of histone methylation by noncoding RNAs[J].Biochim Biophys Acta,2014,1839(12):1385-1394.