长链非编码RNA与宫颈癌
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摘要
长链非编码RNA (Long non-coding RNA,lncRNAs)是RNA的其中一员,其结构类似于mRNA,但由于没有保守的开放阅读框,因此不能编码蛋白质。LncRNAs曾被认为是基因转录后的异常现象或噪音,没有任何的生物学功能。随着研究的进一步深入,发现其可作为重要的调控分子参与人类正常或异常的生物学活动过程。LncRNAs与神经系统功能、机体代谢紊乱以及肿瘤等疾病的发生发展密切相关。异常表达于宫颈癌的lncRNAs通过发挥抑制肿瘤或促进肿瘤的作用,参与调控宫颈癌的各个生物学过程。文中结合最新报道就lncRNAs在宫颈癌的异常调节、分子调节机制和潜在临床应用方面进行综述。
Long non-coding RNAs(lncRNAs) are members of RNA that are structurally similar to mRNA. They cannot encode proteins because they do not have a conserved open reading frame. LncRNAs were once regarded as abnormalities or noises or without any biological function after gene transcription. With the further development of research, it has been found that it can participate in normal or abnormal biological processes as an important regulator. LncRNAs are closely related to the development of nervous system function, metabolic disorders and tumors. LncRNAs abnormally expressed in cervical cancer participate in the regulation of various biological processes of cervical cancer by inhibiting or promoting tumors. This article reviews the recent reports on the abnormal regulation, molecular regulation mechanism and potential clinical application of lncRNAs in cervical cancer.
Long non-coding RNAs(lncRNAs) are members of RNA that are structurally similar to mRNA. They cannot encode proteins because they do not have a conserved open reading frame. LncRNAs were once regarded as abnormalities or noises or without any biological function after gene transcription. With the further development of research, it has been found that it can participate in normal or abnormal biological processes as an important regulator. LncRNAs are closely related to the development of nervous system function, metabolic disorders and tumors. LncRNAs abnormally expressed in cervical cancer participate in the regulation of various biological processes of cervical cancer by inhibiting or promoting tumors. This article reviews the recent reports on the abnormal regulation, molecular regulation mechanism and potential clinical application of lncRNAs in cervical cancer.
引文
[1]Xia Y,Zhang T,Zhang ZX,et al.Gene,human papillomavirus and serum related protein detection in New progress of the application of cervical cancer diagnosis.J Chin Pract Diagn Ther,2008,22(12):924-927(in Chinese).夏燕,张钿,张朝霞,等.基因、人乳头瘤病毒和血清蛋白相关检测在宫颈癌诊断中的应用新进展中华实用诊断与治疗杂志,2008,22(12):924-927.
[2]Wang RG,Shen Y,Li Q,et al.DNA damage-induced lncRNA-UCA1 promotes HeLa cell proliferation Chin J Biochem Mol Biol,2015,31(5):505-513(in Chinese).王瑞国,沈远,李清,等.DNA损伤诱导的长链非编码RNA-UCA1促进HeLa细胞增殖.中国生物化学与分子生物学报,2015,31(5):505-513.
[3]Chen GT,Yang X,Cheng YX.Different expression profiles of lncRNA in cervical cancer tissues and its significance.Pract J Cancer,2017,32(4):523-527(in Chinese).陈干涛,杨潇,程艳香.LncRNA在宫颈癌组织中的表达谱变化及意义.实用癌症杂志,2017,32(4):523-527.
[4]Esteller M.Non-coding RNAs in human disease.Nat Rev Genet,2011,12(12):861-874.
[5]Lu HZ,He Y,Lin L,et al.Long non-coding RNAMALAT1 modulates radiosensitivity of HR-HPV+cervical cancer via sponging miR-145.Tumour Biol,2016,37(2):1683-1691.
[6]Heilmann K,Toth R,Bossmann C,et al Genome-wide screen for differentially methylated long noncoding RNAs identifies Esrp2 and lncRNAEsrp2-as regulated by enhancer DNA methylation with prognostic relevance for human breast cancer.Oncogene,2017,36(46):6446-6461.
[7]Ma ZH,Huang H,Wang JR,et al.Long non-coding RNA SNHG15 inhibits P15 and KLF2 expression to promote pancreatic cancer proliferation through EZH2-mediated H3K27me3.Oncotarget,2017,8(48):84153-84167.
[8]Cheng YX,Yang X,Chen GT.Significance of different expression profiles of LncRNA in cervical cancer before and after radiotherapy and chemotherapy.Med J Wuhan Univ,2017,38(2):241-246,333(in Chinese).程艳香,杨潇,陈干涛.宫颈癌放化疗前后LncRNA的表达谱变化及意义.武汉大学学报:医学版,2017,38(2):241-246,333.
[9]Gibb EA,Becker-Santos DD,Enfield KSS,et al.Aberrant expression of long noncoding RNAs in cervical intraepithelial neoplasia.Int J Gynecol Cancer,2012,22(9):1557-1563.
[10]Kunej T,Obsteter J,Pogacar Z,et al.The decalog of long non-coding RNA involvement in cancer diagnosis and monitoring.Crit Rev Clin Lab Sci2014,51(6):344-357.
[11]Dai MY,Chen SY,Wei XM,et al.Diagnosis prognosis and bioinformatics analysis of lncRNAs in hepatocellular carcinoma.Oncotarget,2017,8(56):95799-95809.
[12]Jin XJ,Chen XJ,Hu Y,et al.LncRNA-TCONS_00026907 is involved in the progression and prognosis of cervical cancer through inhibiting miR-143-5p.Cancer Med,2017,6(6):1409-1423.
[13]Fan YY,Nan Y,Huang JJ,et al.Up-regulation of inflammation-related LncRNA-IL7R predicts poor clinical outcome in patients with cervical cancer.Biosci Rep,2018,38(3):BSR20180483.
[14]Zhang J,Yao TT,Wang YX,et al.Long noncoding RNA MEG3 is downregulated in cervical cancer and affects cell proliferation and apoptosis by regulating miR-21.Cancer Biol Ther,2016,17(1):104-113.
[15]Wang XG,Wang ZH,Wang JC,et al.LncRNAMEG3 has anti-activity effects of cervical cancer Biomed Pharmacother,2017,94:636-643.
[16]Zhao LP,Li RH,Han DM,et al.Independent prognostic Factor of low-expressed LncRNAZNF667-AS1 for cervical cancer and inhibitory function on the proliferation of cervical cancer.Eur Rev Med Pharmacol Sci,2017,21(23):5353-5360.
[17]Friedl P,Wolf K.Tumour-cell invasion and migration:diversity and escape mechanisms.Nat Rev Cancer,2003,3(5):362-374.
[18]Gan L,Chen Y,Liu H,et al.Long non-coding RNAZEB1-antisense 1 affects cell migration and invasion of cervical cancer by regulating epithelialmesenchymal transition via the p38MAPK signaling pathway.Gynecol Obstet Invest,2018:1-9.
[19]Huang L,Liao LM,Liu AW,et al.Overexpression of long noncoding RNA HOTAIR predicts a poor prognosis in patients with cervical cancer.Arch Gynecol Obstet,2014,290(4):717-723.
[20]Kim HJ,Lee DW,Yim GW,et al.Long non-coding RNA HOTAIR is associated with human cervical cancer progression.Int J Oncol,2015,46(2):521-530.
[21]Zheng P,Yin Z,Wu Y,et al.LncRNA HOTAIRpromotes cell migration and invasion by regulating MKL1 via inhibition miR206 expression in HeLa cells.Cell Commun Signal,2018,16:5.
[22]Zhu J,Shi HR,Liu HN,et al.Long non-coding RNATUG1 promotes cervical cancer progression by regulating the miR-138-5p-SIRT1 axis.Oncotarget,2017,8(39):65253-65264.
[23]Hu YY,Sun XW,Mao CC,et al.Upregulation of long noncoding RNA TUG1 promotes cervical cancer cell proliferation and migration.Cancer Med,2017,6(2):471-482.
[24]Yang M,Zhai X,Xia BR,et al.Long noncoding RNA CCHE1 promotes cervical cancer cell proliferation via upregulating PCNA.Tumour Biol,2015,36(10):7615-7622.
[25]Li XR.Effects of cell proliferation,cycle,apoptosis and the expression of survivin gene after down-regulating the expression of lncRNA in Hela[D].Zhanjiang:Guangdong Medical University,2018(in Chinese).李相如.lncRNA沉默对Hela细胞survivin基因表达以及细胞增殖、周期和凋亡的影响[D].湛江:广东医科大学,2018.
[26]Jing L,Yuan W,Dong RF,et al.HOTAIR enhanced aggressive biological behaviors and induced radio-resistance via inhibiting p21 in cervical cancer.Tumour Biol,2015,36(5):3611-3619.
[27]Harries LW.Long non-coding RNAs and human disease.Biochem Soc Trans,2012,40(4):902-906.
[28]Lipovich L,Johnson R,Lin CY.MacroRNAunderdogs in a microRNA world:evolutionary,regulatory,and biomedical significance of mammalian long non-protein-coding RNA.Biochim Biophys Acta,2010,1799(9):597-615.
[29]Hu XG,Jiang HJ,Jiang XJ.Downregulation of lncRNA ANRIL inhibits proliferation,induces apoptosis,and enhances radiosensitivity in nasopharyngeal carcinoma cells through regulating miR-125a.Cancer Biol Ther,2017,18(5):331-338.
[30]Iden M,Fye S,Li KG,et al.The lncRNA PVT1contributes to the cervical cancer phenotype and associates with poor patient prognosis.PLoS ONE,2016,11(5):e0156274.
[31]Shen CJ,Cheng YM,Wang CL.LncRNA PVT1epigenetically silences miR-195 and modulates EMTand chemoresistance in cervical cancer cells.J Drug Target,2017,25(7):637-644.
[32]Feng YQ,Zou W,Hu CH,et al.Modulation of CASC2/miR-21/PTEN pathway sensitizes cervical cancer to cisplatin.Arch Biochem Biophys,2017623-624:20-30.
[33]Han DM,Wang JF,Cheng GH.LncRNA NEAT1enhances the radio-resistance of cervical cancer via miR-193b-3p/CCND1 axis.Oncotarget,2018,9(2):2395-2409.
[34]Maass PG,Luft FC,B?hring S.Long non-coding RNA in health and disease.J Mol Med,2014,92(4):337-346.
[35]Shi C,Yang YJ,Yu JP,et al.The long noncoding RNA LINC00473,a target of microRNA 34a,promotes tumorigenesis by inhibiting ILF2degradation in cervical cancer.Am J Cancer Res,2017,7(11):2157-2168.
[36]Hendrickson DG,Hogan DJ,McCullough HL,et al.Concordant regulation of translation and mRNAabundance for hundreds of targets of a human microRNA.PLoS Biol,2009,7(11):e1000238.
[37]Salmena L,Poliseno L,Tay Y,et al.A ceRNAhypothesis:the Rosetta Stone of a hidden RNAlanguage?Cell,2011,146(3):353-358.
[38]Guo HL,Ingolia NT,Weissman JS,et al.Mammalian microRNAs predominantly act to decrease target mRNA levels.Nature,2010,466(7308):835-840.
[39]Gao YL,Zhao ZS,Zhang MY,et al.Long noncoding RNA PVT1 facilitates cervical cancer progression via negative regulating of miR-424.Oncol Res,201725(8):1391-1398.
[40]Hindorff LA,Sethupathy P,Junkins HA,et al Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.Proc Natl Acad Sci USA,2009,106(23):9362-9367.
[41]Verhaegh GW,Verkleij L,Vermeulen SHHM,et al Polymorphisms in the H19 gene and the risk of bladder cancer.Eur Urol,2008,54(5):1118-1126.
[42]Yang YJ,Ren J,Zhang QZ.Distribution of human papilloma virus type 16 E6/E7 gene mutation in cervical precancer or cancer:a case control study in Guizhou Province,China.J Med Virol,2016,88(2):345-350.
[43]Pu Y,Zhang Z,Zhou B,et al.Association of an insertion/deletion polymorphism in IL1A 3?-UTRwith risk for cervical carcinoma in Chinese Han Women.Hum Immunol,2014,75(8):740-744.
[44]Zhang W,Jiang YH,Yu QM,et al.EGFR promoter methylation,EGFR Mutation,and HPV infection in Chinese cervical squamous cell carcinoma.Appl Immunohistochem Mol Morphol,2015,23(9):661-666.
[45]Guo LS,Lu XG,Zheng LJ,et al.Association of long non-coding RNA HOTAIR polymorphisms with cervical cancer risk in a Chinese population.PLoSONE,2016,11(7):e0160039.
[46]Jin H,Lu XY,Ni J,et al.HOTAIR rs7958904polymorphism is associated with increased cervical cancer risk in a Chinese population.Sci Rep,2017,7(1):3144.
[47]Wang Y,Liu Y,Li ZY,et al.Association between MALAT1 and THRIL polymorphisms and precancerous cervical lesions.Genet Test Mol Biomarkers,2018,22(9):509-517.
[48]Cao Y,Liu YL,Lu XY,et al.Upregulation of long noncoding RNA SPRY4-IT1 correlates with tumor progression and poor prognosis in cervical cancer.FEBS Open Bio,2016,6(9):954-960.
[2]Wang RG,Shen Y,Li Q,et al.DNA damage-induced lncRNA-UCA1 promotes HeLa cell proliferation Chin J Biochem Mol Biol,2015,31(5):505-513(in Chinese).王瑞国,沈远,李清,等.DNA损伤诱导的长链非编码RNA-UCA1促进HeLa细胞增殖.中国生物化学与分子生物学报,2015,31(5):505-513.
[3]Chen GT,Yang X,Cheng YX.Different expression profiles of lncRNA in cervical cancer tissues and its significance.Pract J Cancer,2017,32(4):523-527(in Chinese).陈干涛,杨潇,程艳香.LncRNA在宫颈癌组织中的表达谱变化及意义.实用癌症杂志,2017,32(4):523-527.
[4]Esteller M.Non-coding RNAs in human disease.Nat Rev Genet,2011,12(12):861-874.
[5]Lu HZ,He Y,Lin L,et al.Long non-coding RNAMALAT1 modulates radiosensitivity of HR-HPV+cervical cancer via sponging miR-145.Tumour Biol,2016,37(2):1683-1691.
[6]Heilmann K,Toth R,Bossmann C,et al Genome-wide screen for differentially methylated long noncoding RNAs identifies Esrp2 and lncRNAEsrp2-as regulated by enhancer DNA methylation with prognostic relevance for human breast cancer.Oncogene,2017,36(46):6446-6461.
[7]Ma ZH,Huang H,Wang JR,et al.Long non-coding RNA SNHG15 inhibits P15 and KLF2 expression to promote pancreatic cancer proliferation through EZH2-mediated H3K27me3.Oncotarget,2017,8(48):84153-84167.
[8]Cheng YX,Yang X,Chen GT.Significance of different expression profiles of LncRNA in cervical cancer before and after radiotherapy and chemotherapy.Med J Wuhan Univ,2017,38(2):241-246,333(in Chinese).程艳香,杨潇,陈干涛.宫颈癌放化疗前后LncRNA的表达谱变化及意义.武汉大学学报:医学版,2017,38(2):241-246,333.
[9]Gibb EA,Becker-Santos DD,Enfield KSS,et al.Aberrant expression of long noncoding RNAs in cervical intraepithelial neoplasia.Int J Gynecol Cancer,2012,22(9):1557-1563.
[10]Kunej T,Obsteter J,Pogacar Z,et al.The decalog of long non-coding RNA involvement in cancer diagnosis and monitoring.Crit Rev Clin Lab Sci2014,51(6):344-357.
[11]Dai MY,Chen SY,Wei XM,et al.Diagnosis prognosis and bioinformatics analysis of lncRNAs in hepatocellular carcinoma.Oncotarget,2017,8(56):95799-95809.
[12]Jin XJ,Chen XJ,Hu Y,et al.LncRNA-TCONS_00026907 is involved in the progression and prognosis of cervical cancer through inhibiting miR-143-5p.Cancer Med,2017,6(6):1409-1423.
[13]Fan YY,Nan Y,Huang JJ,et al.Up-regulation of inflammation-related LncRNA-IL7R predicts poor clinical outcome in patients with cervical cancer.Biosci Rep,2018,38(3):BSR20180483.
[14]Zhang J,Yao TT,Wang YX,et al.Long noncoding RNA MEG3 is downregulated in cervical cancer and affects cell proliferation and apoptosis by regulating miR-21.Cancer Biol Ther,2016,17(1):104-113.
[15]Wang XG,Wang ZH,Wang JC,et al.LncRNAMEG3 has anti-activity effects of cervical cancer Biomed Pharmacother,2017,94:636-643.
[16]Zhao LP,Li RH,Han DM,et al.Independent prognostic Factor of low-expressed LncRNAZNF667-AS1 for cervical cancer and inhibitory function on the proliferation of cervical cancer.Eur Rev Med Pharmacol Sci,2017,21(23):5353-5360.
[17]Friedl P,Wolf K.Tumour-cell invasion and migration:diversity and escape mechanisms.Nat Rev Cancer,2003,3(5):362-374.
[18]Gan L,Chen Y,Liu H,et al.Long non-coding RNAZEB1-antisense 1 affects cell migration and invasion of cervical cancer by regulating epithelialmesenchymal transition via the p38MAPK signaling pathway.Gynecol Obstet Invest,2018:1-9.
[19]Huang L,Liao LM,Liu AW,et al.Overexpression of long noncoding RNA HOTAIR predicts a poor prognosis in patients with cervical cancer.Arch Gynecol Obstet,2014,290(4):717-723.
[20]Kim HJ,Lee DW,Yim GW,et al.Long non-coding RNA HOTAIR is associated with human cervical cancer progression.Int J Oncol,2015,46(2):521-530.
[21]Zheng P,Yin Z,Wu Y,et al.LncRNA HOTAIRpromotes cell migration and invasion by regulating MKL1 via inhibition miR206 expression in HeLa cells.Cell Commun Signal,2018,16:5.
[22]Zhu J,Shi HR,Liu HN,et al.Long non-coding RNATUG1 promotes cervical cancer progression by regulating the miR-138-5p-SIRT1 axis.Oncotarget,2017,8(39):65253-65264.
[23]Hu YY,Sun XW,Mao CC,et al.Upregulation of long noncoding RNA TUG1 promotes cervical cancer cell proliferation and migration.Cancer Med,2017,6(2):471-482.
[24]Yang M,Zhai X,Xia BR,et al.Long noncoding RNA CCHE1 promotes cervical cancer cell proliferation via upregulating PCNA.Tumour Biol,2015,36(10):7615-7622.
[25]Li XR.Effects of cell proliferation,cycle,apoptosis and the expression of survivin gene after down-regulating the expression of lncRNA in Hela[D].Zhanjiang:Guangdong Medical University,2018(in Chinese).李相如.lncRNA沉默对Hela细胞survivin基因表达以及细胞增殖、周期和凋亡的影响[D].湛江:广东医科大学,2018.
[26]Jing L,Yuan W,Dong RF,et al.HOTAIR enhanced aggressive biological behaviors and induced radio-resistance via inhibiting p21 in cervical cancer.Tumour Biol,2015,36(5):3611-3619.
[27]Harries LW.Long non-coding RNAs and human disease.Biochem Soc Trans,2012,40(4):902-906.
[28]Lipovich L,Johnson R,Lin CY.MacroRNAunderdogs in a microRNA world:evolutionary,regulatory,and biomedical significance of mammalian long non-protein-coding RNA.Biochim Biophys Acta,2010,1799(9):597-615.
[29]Hu XG,Jiang HJ,Jiang XJ.Downregulation of lncRNA ANRIL inhibits proliferation,induces apoptosis,and enhances radiosensitivity in nasopharyngeal carcinoma cells through regulating miR-125a.Cancer Biol Ther,2017,18(5):331-338.
[30]Iden M,Fye S,Li KG,et al.The lncRNA PVT1contributes to the cervical cancer phenotype and associates with poor patient prognosis.PLoS ONE,2016,11(5):e0156274.
[31]Shen CJ,Cheng YM,Wang CL.LncRNA PVT1epigenetically silences miR-195 and modulates EMTand chemoresistance in cervical cancer cells.J Drug Target,2017,25(7):637-644.
[32]Feng YQ,Zou W,Hu CH,et al.Modulation of CASC2/miR-21/PTEN pathway sensitizes cervical cancer to cisplatin.Arch Biochem Biophys,2017623-624:20-30.
[33]Han DM,Wang JF,Cheng GH.LncRNA NEAT1enhances the radio-resistance of cervical cancer via miR-193b-3p/CCND1 axis.Oncotarget,2018,9(2):2395-2409.
[34]Maass PG,Luft FC,B?hring S.Long non-coding RNA in health and disease.J Mol Med,2014,92(4):337-346.
[35]Shi C,Yang YJ,Yu JP,et al.The long noncoding RNA LINC00473,a target of microRNA 34a,promotes tumorigenesis by inhibiting ILF2degradation in cervical cancer.Am J Cancer Res,2017,7(11):2157-2168.
[36]Hendrickson DG,Hogan DJ,McCullough HL,et al.Concordant regulation of translation and mRNAabundance for hundreds of targets of a human microRNA.PLoS Biol,2009,7(11):e1000238.
[37]Salmena L,Poliseno L,Tay Y,et al.A ceRNAhypothesis:the Rosetta Stone of a hidden RNAlanguage?Cell,2011,146(3):353-358.
[38]Guo HL,Ingolia NT,Weissman JS,et al.Mammalian microRNAs predominantly act to decrease target mRNA levels.Nature,2010,466(7308):835-840.
[39]Gao YL,Zhao ZS,Zhang MY,et al.Long noncoding RNA PVT1 facilitates cervical cancer progression via negative regulating of miR-424.Oncol Res,201725(8):1391-1398.
[40]Hindorff LA,Sethupathy P,Junkins HA,et al Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.Proc Natl Acad Sci USA,2009,106(23):9362-9367.
[41]Verhaegh GW,Verkleij L,Vermeulen SHHM,et al Polymorphisms in the H19 gene and the risk of bladder cancer.Eur Urol,2008,54(5):1118-1126.
[42]Yang YJ,Ren J,Zhang QZ.Distribution of human papilloma virus type 16 E6/E7 gene mutation in cervical precancer or cancer:a case control study in Guizhou Province,China.J Med Virol,2016,88(2):345-350.
[43]Pu Y,Zhang Z,Zhou B,et al.Association of an insertion/deletion polymorphism in IL1A 3?-UTRwith risk for cervical carcinoma in Chinese Han Women.Hum Immunol,2014,75(8):740-744.
[44]Zhang W,Jiang YH,Yu QM,et al.EGFR promoter methylation,EGFR Mutation,and HPV infection in Chinese cervical squamous cell carcinoma.Appl Immunohistochem Mol Morphol,2015,23(9):661-666.
[45]Guo LS,Lu XG,Zheng LJ,et al.Association of long non-coding RNA HOTAIR polymorphisms with cervical cancer risk in a Chinese population.PLoSONE,2016,11(7):e0160039.
[46]Jin H,Lu XY,Ni J,et al.HOTAIR rs7958904polymorphism is associated with increased cervical cancer risk in a Chinese population.Sci Rep,2017,7(1):3144.
[47]Wang Y,Liu Y,Li ZY,et al.Association between MALAT1 and THRIL polymorphisms and precancerous cervical lesions.Genet Test Mol Biomarkers,2018,22(9):509-517.
[48]Cao Y,Liu YL,Lu XY,et al.Upregulation of long noncoding RNA SPRY4-IT1 correlates with tumor progression and poor prognosis in cervical cancer.FEBS Open Bio,2016,6(9):954-960.