lncRNA与肝癌相关性研究进展
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摘要
肝癌是发病率和病死率均较高的恶性肿瘤之一,据统计,中国每年的肝癌新发病例约占世界水平的一半。传统的肝癌诊断标志物,敏感性和特异性均不理想,不利于早期肝癌的诊断及治疗。lncRNA是近年来被高度关注的"明星基因",已被公认参与多种肿瘤的发生、发展及预后,同样与肝癌关系密切。由于许多lncRNA在组织中的特异性表达,lncRNA已经被广泛的认为是某些特定的病理环境下的生物标志物或治疗的靶点。本文重点阐述lncRNA分子水平生物学功能,及总结常见lncRNA与肝癌相关性研究。
Liver cancer is one of the malignant tumors with high morbidity and mortality. According to statistics,the proportion for the new cases of liver cancer each year in China accounts for half of the world level. While neither the sensitivity nor the specificity of traditional diagnostic biomarkers of liver cancer are desirable, which is not conducive to the diagnosis and treatment of early liver cancer. lncRNA is a star gene with highly concerns in recent years. It has been accepted to be involved in the occurrence, development, and prognosis of multiple tumors, as well as liver cancer. Because of the specific expressions of many lncRNAs in tissues, it has been widely recognized as a biomarker or therapeutic target in certain pathological conditions. This review focused on the biological functions of lncRNA at molecular level, and summarized the correlation studies between some common lncRNAs and liver cancer.
Liver cancer is one of the malignant tumors with high morbidity and mortality. According to statistics,the proportion for the new cases of liver cancer each year in China accounts for half of the world level. While neither the sensitivity nor the specificity of traditional diagnostic biomarkers of liver cancer are desirable, which is not conducive to the diagnosis and treatment of early liver cancer. lncRNA is a star gene with highly concerns in recent years. It has been accepted to be involved in the occurrence, development, and prognosis of multiple tumors, as well as liver cancer. Because of the specific expressions of many lncRNAs in tissues, it has been widely recognized as a biomarker or therapeutic target in certain pathological conditions. This review focused on the biological functions of lncRNA at molecular level, and summarized the correlation studies between some common lncRNAs and liver cancer.
引文
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[8] HON C C, RAMILOWSKI J A, HARSHBARGER J, et al. An atlas of human long non-coding RNAs with accurate 5 ends [J]. Nature, 2017, 543(7644): 199-204. DOI: 10.1038/nature21374.
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[10] KRETZ M, SIPRASHVILI Z, CHU C, et al. Control of somatic tissue differentiation by the long non-coding RNA TINCR [J]. Nature, 2013, 493(7431): 231-235. DOI: 10.1038/nature11661.
[11] HEZRONI H, KOPPSTEIN D, SCHWARTZ M G, et al. Principles of long noncoding RNA evolution derived from direct comparison of transcriptomes in 17 species [J]. Cell Rep, 2015, 11(7): 1110-1122. DOI: 10.1016/j.celrep.2015.04.023.
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[14] SCHMITT A M, CHANG H Y. Long noncoding RNAs in cancer pathways [J]. Cancer Cell, 2016, 29(4): 452. DOI: 10.1016/j.ccell.2016.03.010.
[15] PRENSNER J R, IYER M K, SAHU A, et al. The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex [J]. Nat Genet, 2013, 45(11): 1392-1398. DOI: 10.1038/ng.2771.
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[17] PONTING C P, OLIVER P L, REIK W. Evolution and functions of long noncoding RNAs [J]. Cell, 2009, 136(4): 629-641. DOI: 10.1016/j.cell.2009.02.006.
[18] BERTONE P, STOLC V, ROYCE T E, et al. Global identification of human transcribed sequences with genome tiling arrays [J]. Science, 2004, 306(5705): 2242-2246. DOI: 10.1126/science.1103388.
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[22] EBERT M S, NEILSON J R, SHARP P A. MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells [J]. Nat Methods, 2007, 4(9): 721-726. DOI: 10.1038/nmeth1079.
[23] PLATH K, FANG J, MLYNARCZYK-EVANS S K, et al. Role of histone H3 lysine 27 methylation in X inactivation [J]. Science, 2003, 300(5616): 131-135. DOI: 10.1126/science.1084274.
[24] DA ROCHA S T, BOEVA V, ESCAMILLA-DEL-ARENAL M, et al. Jarid2 is implicated in the initial Xist-induced targeting of PRC2 to the inactive X chromosome [J]. Mol Cell, 2014, 53(2): 301-316. DOI: 10.1016/j.molcel.2014.01.002.
[25] ZHAO J, SUN B K, ERWIN J A, et al. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome [J]. Science, 2008, 322(5902): 750-756. DOI: 10.1126/science.1163045.
[26] HUANG J Z, CHEN M, CHEN, et al. Apeptide encoded by a putative lncRNA HOXB-AS3 suppersses colon cancer growth [J]. Mol Cell, 2017, 68(1): 171-184. DOI: 10.1016/j.molcel.2017.09.015.
[27] YUAN J H, YANG F, WANG F, et al. A long noncoding RNA activated by TGFbeta promotes the invasion-metastasis cascade in hepatocellular carcinoma [J]. Cancer Cell, 2015, 25(5): 666-681. DOI: 10.1016/j.ccr.2014.03.010.
[28] XIE H, MA H, ZHOU D. Plasma HULC as a promising novel biomarker for the detection of hepatocellular carcinoma [J]. Bio Med Researc Int, 2013: 136106. DOI: 10.1155/2013/136106.
[29] PANZITT K, TSCHERNATSCH M M, GUELLY C, et al. Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA [J]. Gastroenterology, 2007, 132(1): 330-342. DOI: 10.1053/j.gastro.2006.08.026.
[30] WANG J, LIU X, WU H, et al. CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer [J]. Nucleic Acids Res, 2010, 38(16): 5366-5383. DOI: 10.1093/nar/gkq285.
[31] DU Y, KONG G, YOU X, et al. Elevation of highly up-regulated in liver cancer (HULC) by hepatitis B virus X protein promotes hepatoma cell proliferation via down-regulating p18 [J]. J Biol Chem, 2012, 287(31): 26302-26311. DOI: 10.1074/jbc.M112.342113.
[32] MAASS P G, LUFT F C, B?HRINGS. Long non-coding RNA in health and disease [J]. J Mol Med (Berl), 2014, 92(4): 337-346. DOI: 10.1007/s00109-014-1131-8.
[33] LI H, AN J, WU M, et al. LncRNA HOTAIR promotes human liver cancer stem cell malignant growth through downregulation of SETD2 [J]. Oncotarget, 2015, 6(29): 27847-27864. DOI: 10.18632/oncotarget.4443.
[34] PU H, ZHENG Q, LI H, et al. CUDR promotes liver cancer stem cell growth through upregulating TERT and C-Myc [J]. Oncotarget, 2015, 6(38): 40775-40798. DOI: 10.18632/oncotarget.5805.
[35] LESLIE N R, DOWNES C P. PTEN function: how normal cells control it and tumour cells lose it [J]. Biochem J, 2004, 382(Pt1): 1-11. DOI: 10.1042/ BJ20040825.
[36] WANG Y, HE L, DU Y, et al. The long noncoding RNA lncTCF7 promotes self-renewal of human liver cancer stem cells through activation of Wnt signaling [J]. Cell Stem Cell, 2015, 16(4): 413-425. DOI: 10.1016/j.stem.2015.03.003.
[37] MELLO S S, SINOW C, RAJ N, et al. Neat1 is a p53-inducible lincRNA essential-for transformation suppression [J]. Genes Dev, 2017, 31(11): 1095-1108. DOI: 10.1101/gad.284661.116.
[38] CHAKRAVARTY D, SBONER A, NAIR S S, et al. The oestrogen receptor alpharegulated lncRNA NEAT1 is a critical modulator of prostate cancer [J]. Nat Commu, 2014, 5: 5383. DOI: 10.1038/ncomms6383.
[39] ADRIAENS C, BARRA J, LATIL M, et al. p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity [J]. Nat Med, 2016, 22(8): 861-868. DOI: 10.1038/ nm.4135.
[40] YU W, QIAO Y, TANG X, et al. Suppressor long non-coding RNA, MT1DP is negatively regulated by YAP and Runx2 to inhibit FoxA1 in liver cancer cells [J]. Cell Signal, 2014, 26(12): 2961-2968. DOI: 10.1016/j.cellsig.2014.09.011.
[41] DING L J, LI Y, WANG S D , et al. Long noncoding RNA lncCAMTA1 promotes proliferation and cancer stem cell-like properties of liver cancer by inhibiting CAMTA1 [J]. Int J Mol Sci, 2016, 17(10): pii: E1617. DOI: 10.3390/ijms17101617.
[42] WANG X, SUN W, SHEN W, et al. Long non-coding RNA DILC regulates liver cancer stem cells via IL-6/STAT3 axis [J]. J Hepatol, 2016, 64(6): 1283-1294. DOI: 10.1016/j.jhep.2016.01.019.
[43] WAHLESTEDT C. Targeting long non-coding RNA to therapeutically upregulate gene expression [J]. Nat Rev Drug Discov, 2013, 12(6): 433-446. DOI: 10.1038/nrd4018.
[44] ARUN G, DIERMEIER S, AKERMAN M, et al. Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss [J]. Genes Dev, 2016, 30(1): 34-51.DOI: 10.1101/gad.270959.115.
[45] YAN X, HU Z, FENG Y, et al. Comprehensive genomic characterization of long non-coding RNAs across human cancers [J]. Cancer Cell, 2015, 28(4): 529-540. DOI: 10.1016/j.ccell.2015.09.006.
[46] BRUNNER A L, BECK A H, EDRIS B, et al. Transcriptional profiling of long non-coding RNAs and novel transcribed regions across a diverse panel of archived human cancers [J]. Genome Biol, 2012,13(8): R75. DOI: 10.1186/gb-2012-13-8-r75.
[2] KAPRANOV P, CHENG J, DIKE S, et al. RNA maps reveal new RNA classes and a possible function for pervasive transcription [J]. Science, 2007, 316(5830): 1484-1488. DOI: 10.1126/science.1138341.
[3] WILLINGHAM A T, GINGERAS T R. TUF love for“junk”DNA [J]. Cell, 2006, 125(7): 1215-1220. DOI: 10.1016/j.cell.2006.06.009.
[4] WILUSZ J E, SUNWOO H, SPECTOR D L. Long noncoding RNAs:functional surprises from the RNA world [J]. Genes Dev, 2009, 23(13): 1494-1504. DOI: 10.1101/gad.1800909.
[5] DIECI G, FIORINO G, CASTELNUOVO M, et al. The expanding RNA polymerase Ⅲ transcriptome [J]. Trends Genet, 2007, 23(12): 614-622. DOI: 10.1016/j.tig.2007. 09.001.
[6] MARTONE R, EUSKIRCHEN G, BERTONE P, et al. Distribution of NF-kappaB-binding sites across human chromosome 22 [J]. Proc Natl Acad Sci USA, 2003, 100(21): 12247-12252. DOI: 10.1073/pnas.2135255100.
[7] ROEDER R G, RUTTER W J. Specific nucleolar and nucleoplasmic RNA polymerases [J]. Natl Acad Sci USA, 1970, 65(3): 675-682.
[8] HON C C, RAMILOWSKI J A, HARSHBARGER J, et al. An atlas of human long non-coding RNAs with accurate 5 ends [J]. Nature, 2017, 543(7644): 199-204. DOI: 10.1038/nature21374.
[9] RANSOHOFF J D, WEI Y, KHAVARI P A. The functions and unique features of long intergenic non-coding RNA [J]. Nat Rev Mol Cell Biol, 2018, 19(3): 143-157. DOI: 10.1038/nrm.2017.104.
[10] KRETZ M, SIPRASHVILI Z, CHU C, et al. Control of somatic tissue differentiation by the long non-coding RNA TINCR [J]. Nature, 2013, 493(7431): 231-235. DOI: 10.1038/nature11661.
[11] HEZRONI H, KOPPSTEIN D, SCHWARTZ M G, et al. Principles of long noncoding RNA evolution derived from direct comparison of transcriptomes in 17 species [J]. Cell Rep, 2015, 11(7): 1110-1122. DOI: 10.1016/j.celrep.2015.04.023.
[12] QUINN J J, ZHANG Q C, GEORQIEV P, et al. Rapid evolutionary turnover underlies conserved lncRNA-genome interactions [J]. Genes Dev, 2016, 30(2): 191-207. DOI: 10.1101/gad.272187.115.
[13] ULITSKY I, SHKUMATAVA A, C H JAN, et al. Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution [J]. Cell, 2 011, 147(7): 1537-1550. DOI: 10.1016/j.cell.2011.11.055.
[14] SCHMITT A M, CHANG H Y. Long noncoding RNAs in cancer pathways [J]. Cancer Cell, 2016, 29(4): 452. DOI: 10.1016/j.ccell.2016.03.010.
[15] PRENSNER J R, IYER M K, SAHU A, et al. The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex [J]. Nat Genet, 2013, 45(11): 1392-1398. DOI: 10.1038/ng.2771.
[16] SCHMITZ S U, PHILLIP G, HERRMANN B G. Mechanisms of long noncoding RNA function in development and disease [J]. Cell Mol Life Sci, 2016, 73(13): 2491-2509. DOI:10.1007/s00018-016-2174-5.
[17] PONTING C P, OLIVER P L, REIK W. Evolution and functions of long noncoding RNAs [J]. Cell, 2009, 136(4): 629-641. DOI: 10.1016/j.cell.2009.02.006.
[18] BERTONE P, STOLC V, ROYCE T E, et al. Global identification of human transcribed sequences with genome tiling arrays [J]. Science, 2004, 306(5705): 2242-2246. DOI: 10.1126/science.1103388.
[19] PONJAVIC J, PONTING C P, LUNTER G. Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs [J]. Genome Res, 2007, 17(5): 556-565. DOI: 10.1101/gr.6036807.
[20] RAMOS A D, ANDERSEN R E, LIU S J, et al. The long noncoding RNA Pnky regulates neuronal differentiation of embryonic and postnatal neural stem cells [J]. Cell Stem Cell, 2015, 16(4): 439-447. DOI: 10.1016/j.stem.2015.02.007.
[21] TRIPATHI V, ELLIS J D, SHEN Z, et al. The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation [J]. Mol Cell, 2010, 39(6): 925-938. DOI: 10.1016/ j.molcel.2010.08.011.
[22] EBERT M S, NEILSON J R, SHARP P A. MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells [J]. Nat Methods, 2007, 4(9): 721-726. DOI: 10.1038/nmeth1079.
[23] PLATH K, FANG J, MLYNARCZYK-EVANS S K, et al. Role of histone H3 lysine 27 methylation in X inactivation [J]. Science, 2003, 300(5616): 131-135. DOI: 10.1126/science.1084274.
[24] DA ROCHA S T, BOEVA V, ESCAMILLA-DEL-ARENAL M, et al. Jarid2 is implicated in the initial Xist-induced targeting of PRC2 to the inactive X chromosome [J]. Mol Cell, 2014, 53(2): 301-316. DOI: 10.1016/j.molcel.2014.01.002.
[25] ZHAO J, SUN B K, ERWIN J A, et al. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome [J]. Science, 2008, 322(5902): 750-756. DOI: 10.1126/science.1163045.
[26] HUANG J Z, CHEN M, CHEN, et al. Apeptide encoded by a putative lncRNA HOXB-AS3 suppersses colon cancer growth [J]. Mol Cell, 2017, 68(1): 171-184. DOI: 10.1016/j.molcel.2017.09.015.
[27] YUAN J H, YANG F, WANG F, et al. A long noncoding RNA activated by TGFbeta promotes the invasion-metastasis cascade in hepatocellular carcinoma [J]. Cancer Cell, 2015, 25(5): 666-681. DOI: 10.1016/j.ccr.2014.03.010.
[28] XIE H, MA H, ZHOU D. Plasma HULC as a promising novel biomarker for the detection of hepatocellular carcinoma [J]. Bio Med Researc Int, 2013: 136106. DOI: 10.1155/2013/136106.
[29] PANZITT K, TSCHERNATSCH M M, GUELLY C, et al. Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA [J]. Gastroenterology, 2007, 132(1): 330-342. DOI: 10.1053/j.gastro.2006.08.026.
[30] WANG J, LIU X, WU H, et al. CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer [J]. Nucleic Acids Res, 2010, 38(16): 5366-5383. DOI: 10.1093/nar/gkq285.
[31] DU Y, KONG G, YOU X, et al. Elevation of highly up-regulated in liver cancer (HULC) by hepatitis B virus X protein promotes hepatoma cell proliferation via down-regulating p18 [J]. J Biol Chem, 2012, 287(31): 26302-26311. DOI: 10.1074/jbc.M112.342113.
[32] MAASS P G, LUFT F C, B?HRINGS. Long non-coding RNA in health and disease [J]. J Mol Med (Berl), 2014, 92(4): 337-346. DOI: 10.1007/s00109-014-1131-8.
[33] LI H, AN J, WU M, et al. LncRNA HOTAIR promotes human liver cancer stem cell malignant growth through downregulation of SETD2 [J]. Oncotarget, 2015, 6(29): 27847-27864. DOI: 10.18632/oncotarget.4443.
[34] PU H, ZHENG Q, LI H, et al. CUDR promotes liver cancer stem cell growth through upregulating TERT and C-Myc [J]. Oncotarget, 2015, 6(38): 40775-40798. DOI: 10.18632/oncotarget.5805.
[35] LESLIE N R, DOWNES C P. PTEN function: how normal cells control it and tumour cells lose it [J]. Biochem J, 2004, 382(Pt1): 1-11. DOI: 10.1042/ BJ20040825.
[36] WANG Y, HE L, DU Y, et al. The long noncoding RNA lncTCF7 promotes self-renewal of human liver cancer stem cells through activation of Wnt signaling [J]. Cell Stem Cell, 2015, 16(4): 413-425. DOI: 10.1016/j.stem.2015.03.003.
[37] MELLO S S, SINOW C, RAJ N, et al. Neat1 is a p53-inducible lincRNA essential-for transformation suppression [J]. Genes Dev, 2017, 31(11): 1095-1108. DOI: 10.1101/gad.284661.116.
[38] CHAKRAVARTY D, SBONER A, NAIR S S, et al. The oestrogen receptor alpharegulated lncRNA NEAT1 is a critical modulator of prostate cancer [J]. Nat Commu, 2014, 5: 5383. DOI: 10.1038/ncomms6383.
[39] ADRIAENS C, BARRA J, LATIL M, et al. p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity [J]. Nat Med, 2016, 22(8): 861-868. DOI: 10.1038/ nm.4135.
[40] YU W, QIAO Y, TANG X, et al. Suppressor long non-coding RNA, MT1DP is negatively regulated by YAP and Runx2 to inhibit FoxA1 in liver cancer cells [J]. Cell Signal, 2014, 26(12): 2961-2968. DOI: 10.1016/j.cellsig.2014.09.011.
[41] DING L J, LI Y, WANG S D , et al. Long noncoding RNA lncCAMTA1 promotes proliferation and cancer stem cell-like properties of liver cancer by inhibiting CAMTA1 [J]. Int J Mol Sci, 2016, 17(10): pii: E1617. DOI: 10.3390/ijms17101617.
[42] WANG X, SUN W, SHEN W, et al. Long non-coding RNA DILC regulates liver cancer stem cells via IL-6/STAT3 axis [J]. J Hepatol, 2016, 64(6): 1283-1294. DOI: 10.1016/j.jhep.2016.01.019.
[43] WAHLESTEDT C. Targeting long non-coding RNA to therapeutically upregulate gene expression [J]. Nat Rev Drug Discov, 2013, 12(6): 433-446. DOI: 10.1038/nrd4018.
[44] ARUN G, DIERMEIER S, AKERMAN M, et al. Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss [J]. Genes Dev, 2016, 30(1): 34-51.DOI: 10.1101/gad.270959.115.
[45] YAN X, HU Z, FENG Y, et al. Comprehensive genomic characterization of long non-coding RNAs across human cancers [J]. Cancer Cell, 2015, 28(4): 529-540. DOI: 10.1016/j.ccell.2015.09.006.
[46] BRUNNER A L, BECK A H, EDRIS B, et al. Transcriptional profiling of long non-coding RNAs and novel transcribed regions across a diverse panel of archived human cancers [J]. Genome Biol, 2012,13(8): R75. DOI: 10.1186/gb-2012-13-8-r75.