The regulatory mechanisms by enhancers during cancer initiation and progression
Received date: 2021-12-31
Revised date: 2022-03-05
Online published: 2022-03-15
Supported by
Supported by the National Natural Science Foundation of China Nos(82072499);Supported by the National Natural Science Foundation of China Nos(31801094);Young Scientist Innovation Team Support Program of Beihang University No(YWF-21-BJ-J-T105)
Enhancer is a DNA sequence, and mainly acts in cis to regulate gene transcription. Due to the uncertainty in both location and distance between enhancers and their target genes, it is more complex and difficult to study the underlying regulatory mechanism of enhancers. Accumulating evidences indicate that enhancers are closely associated with the occurrence and development of diseases, such as cancer. Therefore, the studies of enhancers in cancer will be helpful to deeply unravel cancer pathogenesis and to promote the development of antitumor drugs. The related research is with great social significance and economic value. Currently, the identification of enhancers is insufficient. The regulatory mechanisms by enhancers during the initiation and progression of cancer and other diseases have not been fully delineated. In this review, we provide an overview of enhancers, super enhancers and their properties, followed by a description of enhancer prediction and identification at the genome-wide level. Finally, we summarize the regulatory roles of enhancers during diseases such as cancer in recent years, thereby providing a reference for the future exploration on enhancer regulatory mechanisms as well as cancer diagnosis and treatment.
Key words: enhancers; super enhancers; cancer; regulatory mechanisms
Sihan Qi, Qilin Wang, Junyou Zhang, Qian Liu, Chunyan Li . The regulatory mechanisms by enhancers during cancer initiation and progression[J]. Hereditas(Beijing), 2022 , 44(4) : 275 -288 . DOI: 10.16288/j.yczz.21-440
| [1] | Spitz F, Furlong EEM. Transcription factors: from enhancer binding to developmental control. Nat Rev Genet, 2012, 13(9):613-626. |
| [2] | Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, Tanzer A, Lagarde J, Lin W, Schlesinger F, Xue CH, Marinov GK, Khatun J, Williams BA, Zaleski C, Rozowsky J, Röder M, Kokocinski F, Abdelhamid RF, Alioto T, Antoshechkin I, Baer MT, Bar NS, Batut P, Bell K, Bell I, Chakrabortty S, Chen X, Chrast J, Curado J, Derrien T, Drenkow J, Dumais E, Dumais J, Duttagupta R, Falconnet E, Fastuca M, Fejes-Toth K, Ferreira P, Foissac S, Fullwood MJ, Gao H, Gonzalez D, Gordon A, Gunawardena H, Howald C, Jha S, Johnson R, Kapranov P, King B, Kingswood C, Luo OJ, Park E, Persaud K, Preall JB, Ribeca P, Risk B, Robyr D, Sammeth M, Schaffer L, See LH, Shahab A, Skancke J, Suzuki AM, Takahashi H, Tilgner H, Trout D, Walters N, Wang H, Wrobel J, Yu YB, Ruan X, Hayashizaki Y, Harrow J, Gerstein M, Hubbard T, Reymond A, Antonarakis SE, Hannon G, Giddings MC, Ruan YJ, Wold B, Carninci P, Guigó R, Gingeras TR. Landscape of transcription in human cells. Nature, 2012, 489(7414):101-108. |
| [3] | Arrowsmith CH, Bountra C, Fish PV, Lee K, Schapira M. Epigenetic protein families: a new frontier for drug discovery. Nat Rev Drug Discov, 2012, 11(5):384-400. |
| [4] | Schaffner W. Enhancers, enhancers-from their discovery to today’s universe of transcription enhancers. Biol Chem, 2015, 396(4):311-327. |
| [5] | Zabidi MA, Stark A. Regulatory enhancer-core-promoter communication via transcription factors and cofactors. Trends Genet, 2016, 32(12):801-814. |
| [6] | Sagai T, Hosoya M, Mizushina Y, Tamura M, Shiroishi T. Elimination of a long-range cis-regulatory module causes complete loss of limb-specific Shh expression and truncation of the mouse limb. Development, 2005, 132(4):797-803. |
| [7] | Kyrchanova O, Georgiev P. Mechanisms of enhancer- promoter interactions in higher eukaryotes. Int J Mol Sci, 2021, 22(2):671. |
| [8] | Banerji J, Rusconi S, Schaffner W. Expression of a β-globin gene is enhanced by remote SV40 DNA sequences. Cell, 1981, 27(2 Pt 1):299-308. |
| [9] | Moreau P, Hen R, Wasylyk B, Everett R, Gaub MP, Chambon P. The SV40 72 base repair repeat has a striking effect on gene expression both in SV40 and other chimeric recombinants. Nucleic Acids Res, 1981, 9(22):6047-6068. |
| [10] | Bulger M, Groudine M. Functional and mechanistic diversity of distal transcription enhancers. Cell, 2011, 144(3):327-339. |
| [11] | Aerts S. Computational strategies for the genome-wide identification of cis-regulatory elements and transcriptional targets. Curr Top Dev Biol, 2012, 98:121-145. |
| [12] | Di Micco R, Fontanals-Cirera B, Low V, Ntziachristos P, Yuen SK, Lovell CD, Dolgalev I, Yonekubo Y, Zhang GT, Rusinova E, Gerona-Navarro G, Cañamero M, Ohlmeyer M, Aifantis I, Zhou MM, Tsirigos A, Hernando E. Control of embryonic stem cell identity by brd4-dependent transcriptional elongation of super-enhancer-associated pluripotency genes. Cell Rep, 2014, 9(1):234-247. |
| [13] | Mikhaylichenko O, Bondarenko V, Harnett D, Schor IE, Males M, Viales RR, Furlong EEM. The degree of enhancer or promoter activity is reflected by the levels and directionality of eRNA transcription. Genes Dev, 2018, 32(1):42-57. |
| [14] | Andersson R, Gebhard C, Miguel-Escalada I, Hoof I, Bornholdt J, Boyd M, Chen Y, Zhao XB, Schmidl C, Suzuki T, Ntini E, Arner E, Valen E, Li K, Schwarzfischer L, Glatz D, Raithel J, Lilje B, Rapin N, Bagger FO, Jørgensen M, Andersen PR, Bertin N, Rackham O, Burroughs AM, Baillie JK, Ishizu Y, Shimizu Y, Furuhata E, Maeda S, Negishi Y, Mungall CJ, Meehan TF, Lassmann T, Itoh M, Kawaji H, Kondo N, Kawai J, Lennartsson A, Daub CO, Heutink P, Hume DA, Jensen TH, Suzuki H, Hayashizaki Y, Müller F, Forrest ARR, Carninci P, Rehli M, Sandelin A. An atlas of active enhancers across human cell types and tissues. Nature, 2014, 507(7493):455-461. |
| [15] | Kim TK, Hemberg M, Gray JM, Costa AM, Bear DM, Wu J, Harmin DA, Laptewicz M, Barbara-Haley K, Kuersten S, Markenscoff-Papadimitriou E, Kuhl D, Bito H, Worley PF, Kreiman G, Greenberg ME. Widespread transcription at neuronal activity-regulated enhancers. Nature, 2010, 465(7295):182-187. |
| [16] | Visel A, Blow MJ, Li ZR, Zhang T, Akiyama JA, Holt A, Plajzer-Frick I, Shoukry M, Wright C, Chen F, Afzal V, Ren B, Rubin EM, Pennacchio LA. ChIP-seq accurately predicts tissue-specific activity of enhancers. Nature, 2009, 457(7231):854-858. |
| [17] | Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-André V, Sigova AA, Hoke HA, Young RA. Super-enhancers in the control of cell identity and disease. Cell, 2013, 155(4):934-947. |
| [18] | Pott S, Lieb JD. What are super-enhancers? Nat Genet, 2015, 47(1):8-12. |
| [19] | Lovén J, Hoke HA, Lin CY, Lau A, Orlando DA, Vakoc CR, Bradner JE, Lee TI, Young RA. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell, 2013, 153(2):320-334. |
| [20] | Whyte WA, Orlando DA, Hnisz D, Abraham BJ, Lin CY, Kagey MH, Rahl PB, Lee TI, Young RA. Master transcription factors and mediator establish super- enhancers at key cell identity genes. Cell, 2013, 153(2):307-319. |
| [21] | Visel A, Rubin EM, Pennacchio LA. Genomic views of distant-acting enhancers. Nature, 2009, 461(7261):199-205. |
| [22] | Whitaker JW, Nguyen TT, Zhu Y, Wildberg A, Wang W. Computational schemes for the prediction and annotation of enhancers from epigenomic assays. Methods, 2015, 72:86-94. |
| [23] | Pennacchio LA, Bickmore W, Dean A, Nobrega MA, Bejerano G. Enhancers: five essential questions. Nat Rev Genet, 2013, 14(4):288-295. |
| [24] | Pennacchio LA, Ahituv N, Moses AM, Prabhakar S, Nobrega MA, Shoukry M, Minovitsky S, Dubchak I, Holt A, Lewis KD, Plajzer-Frick I, Akiyama J, De Val S, Afzal V, Black BL, Couronne O, Eisen MB, Visel A, Rubin EM. In vivo enhancer analysis of human conserved non-coding sequences. Nature, 2006, 444(7118):499-502. |
| [25] | Lister R, O’Malley RC, Tonti-Filippini J, Gregory BD, Berry CC, Millar AH, Ecker JR. Highly integrated single-base resolution maps of the epigenome in arabidopsis. Cell, 2008, 133(3):523-536. |
| [26] | Emrich SJ, Barbazuk WB, Li L, Schnable PS. Gene discovery and annotation using LCM-454 transcriptome sequencing. Genome Res, 2007, 17(1):69-73. |
| [27] | Stark R, Grzelak M, Hadfield J. RNA sequencing: the teenage years. Nat Rev Genet, 2019, 20(11):631-656. |
| [28] | Wang D, Garcia-Bassets I, Benner C, Li WB, Su X, Zhou YM, Qiu J, Liu W, Kaikkonen MU, Ohgi KA, Glass CK, Rosenfeld MG, Fu XD. Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA. Nature, 2011, 474(7351):390-394. |
| [29] | Core LJ, Martins AL, Danko CG, Waters CT, Siepel A, Lis JT. Analysis of nascent RNA identifies a unified architecture of initiation regions at mammalian promoters and enhancers. Nat Genet, 2014, 46(12):1311-1320. |
| [30] | Schwalb B, Michel M, Zacher B, Frühauf K, Demel C, Tresch A, Gagneur J, Cramer P. TT-seq maps the human transient transcriptome. Science, 2016, 352(6290):1225-1228. |
| [31] | Core LJ, Waterfall JJ, Lis JT. Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters. Science, 2008, 322(5909):1845-1848. |
| [32] | Li WB, Notani D, Ma Q, Tanasa B, Nunez E, Chen AY, Merkurjev D, Zhang J, Ohgi K, Song XY, Oh S, Kim HS, Glass CK, Rosenfeld MG. Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation. Nature, 2013, 498(7455):516-520. |
| [33] | Chen H, Li CY, Peng XX, Zhou ZC, Weinstein JN, Cancer Genome Atlas Research Network, Liang H. A pan-cancer analysis of enhancer expression in nearly 9000 patient samples. Cell, 2018, 173(2):386-399. |
| [34] | Zhang Z, Lee JH, Ruan H, Ye YQ, Krakowiak J, Hu QS, Xiang Y, Gong J, Zhou BY, Wang L, Lin CR, Diao LX, Mills GB, Li WB, Han L. Transcriptional landscape and clinical utility of enhancer RNAs for eRNA-targeted therapy in cancer. Nat Commun, 2019, 10(1):4562. |
| [35] | Buenrostro JD, Giresi PG, Zaba LC, Chang HY, Greenleaf WJ. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat Methods, 2013, 10(12):1213-1218. |
| [36] | Buenrostro JD, Wu BJ, Chang HY, Greenleaf WJ. ATAC-seq: a method for assaying chromatin accessibility genome-wide. Curr Protoc Mol Biol, 2015, 109: 21.29.1-21.29.9. |
| [37] | Orlando V, Strutt H, Paro R. Analysis of chromatin structure by in vivo formaldehyde cross-linking. Methods, 1997, 11(2):205-214. |
| [38] | Mundade R, Ozer HG, Wei H, Prabhu L, Lu T. Role of ChIP-seq in the discovery of transcription factor binding sites, differential gene regulation mechanism, epigenetic marks and beyond. Cell Cycle, 2014, 13(18):2847-2852. |
| [39] | Iwafuchi-Doi M, Donahue G, Kakumanu A, Watts JA, Mahony S, Pugh BF, Lee D, Kaestner KH, Zaret KS. The pioneer transcription factor FoxA maintains an accessible nucleosome configuration at enhancers for tissue-specific gene activation. Mol Cell, 2016, 62(1):79-91. |
| [40] | Creyghton MP, Cheng AW, Welstead GG, Kooistra T, Carey BW, Steine EJ, Hanna J, Lodato MA, Frampton GM, Sharp PA, Boyer LA, Young RA, Jaenisch R. Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci USA, 2010, 107(50):21931-21936. |
| [41] | Rada-Iglesias A, Bajpai R, Swigut T, Brugmann SA, Flynn RA, Wysocka J. A unique chromatin signature uncovers early developmental enhancers in humans. Nature, 2011, 470(7333):279-283. |
| [42] | Skene PJ, Henikoff S. An efficient targeted nuclease strategy for high-resolution mapping of DNA binding sites. Elife, 2017, 6:e21856. |
| [43] | Skene PJ, Henikoff JG, Henikoff S. Targeted in situ genome-wide profiling with high efficiency for low cell numbers. Nat Protoc, 2018, 13(5):1006-1019. |
| [44] | Hainer SJ, Fazzio TG. High-resolution chromatin profiling using CUT&RUN. Curr Protoc Mol Biol, 2019, 126(1):e85. |
| [45] | Ishino Y, Shinagawa H, Makino K, Amemura M, Nakatura A. Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. J Bacteriol, 1987, 169(12):5429-5433. |
| [46] | Jansen R, van Embden JDA, Gaastra W, Schouls LM. Identification of genes that are associated with DNA repeats in prokaryotes. Mol Microbiol, 2002, 43(6):1565-1575. |
| [47] | Gupta D, Bhattacharjee O, Mandal D, Sen MK, Dey D, Dasgupta A, Kazi TA, Gupta R, Sinharoy S, Acharya K, Chattopadhyay D, Ravichandiran V, Roy S, Ghosh D. CRISPR-Cas9 system: a new-fangled dawn in gene editing. Life Sci, 2019, 232:116636. |
| [48] | Jiang F, Doudna JA. CRISPR-Cas9 structures and mechanisms. Annu Rev Biophys, 2017, 46:505-529. |
| [49] | Mali P, Yang LH, Esvelt KM, Aach J, Guell M, DiCarlo JE, Norville JE, Church GM. RNA-guided human genome engineering via Cas9. Science, 2013, 339(6121):823-826. |
| [50] | Cong L, Ran FA, Cox D, Lin SL, Barretto R, Habib N, Hsu PD, Wu XB, Jiang WY, Marraffini LA, Zhang F. Multiplex genome engineering using CRISPR/Cas systems. Science, 2013, 339(6121):819-823. |
| [51] | Korkmaz G, Lopes R, Ugalde AP, Nevedomskaya E, Han R, Myacheva K, Zwart W, Elkon R, Agami R. Functional genetic screens for enhancer elements in the human genome using CRISPR-Cas9. Nat Biotechnol, 2016, 34(2):192-198. |
| [52] | Chen H, Li CY, Zhou ZC, Liang H. Fast-evolving human-specific neural enhancers are associated with aging-related diseases. Cell Syst, 2018, 6(5):604-611. |
| [53] | Wang QL, Liu Q, Qi SH, Zhang JY, Liu X, Li X, Li CY. Comprehensive pan-cancer analyses of pyroptosis-related genes to predict survival and immunotherapeutic outcome. Cancers (Basel), 2022, 14(1):237. |
| [54] | Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3):209-249. |
| [55] | Karczewski KJ, Dudley JT, Kukurba KR, Chen R, Butte AJ, Montgomery SB, Snyder M. Systematic functional regulatory assessment of disease-associated variants. Proc Natl Acad Sci USA, 2013, 110(23):9607-9612. |
| [56] | Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-André V, Sigova AA, Hoke HA, Young RA. Super-enhancers in the control of cell identity and disease. Cell, 2013, 155(4):934-947. |
| [57] | Corradin O, Saiakhova A, Akhtar-Zaidi B, Myeroff L, Willis J, Cowper-Sallari R, Lupien M, Markowitz S, Scacheri PC. Combinatorial effects of multiple enhancer variants in linkage disequilibrium dictate levels of gene expression to confer susceptibility to common traits. Genome Res, 2014, 24(1):1-13. |
| [58] | Gabay M, Li YL, Felsher DW. MYC activation is a hallmark of cancer initiation and maintenance. Cold Spring Harb Perspect Med, 2014, 4(6):a014241. |
| [59] | Herranz D, Ambesi-Impiombato A, Palomero T, Schnell SA, Belver L, Wendorff AA, Xu LY, Castillo-Martin M, Llobet-Navás D, Cordon-Cardo C, Clappier E, Soulier J, Ferrando AA. A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia. Nat Med, 2014, 20(10):1130-1137. |
| [60] | Lancho O, Herranz D. The MYC enhancer-ome: long- range ranscriptional egulation of MYC in cancer. Trends Cancer, 2018, 4(12):810-822. |
| [61] | Herz HM, Hu DQ, Shilatifard A. Enhancer malfunction in cancer. Mol Cell, 2014, 53(6):859-866. |
| [62] | Sur I, Taipale J. The role of enhancers in cancer. Nat Rev Cancer, 2016, 16(8):483-493. |
| [63] | Akhtar-Zaidi B, Cowper-Sallari-lari R, Corradin O, Saiakhova A, Bartels CF, Balasubramanian D, Myeroff L, Lutterbaugh J, Jarrar A, Kalady MF, Willis J, Moore JH, Tesar PJ, Laframboise T, Markowitz S, Lupien M, Scacheri PC. Epigenomic enhancer profiling defines a signature of colon cancer. Science, 2012, 336(6082):736-739. |
| [64] | Zhang XY, Choi PS, Francis JM, Imielinski M, Watanabe H, Cherniack AD, Meyerson M. Identification of focally amplified lineage-specific super-enhancers in human epithelial cancers. Nat Genet, 2016, 48(2):176-182. |
| [65] | Krijger PHL, de Laat W. Regulation of disease-associated gene expression in the 3D genome. Nat Rev Mol Cell Biol, 2016, 17(12):771-782. |
| [66] | Wang XT, Xu J, Zhang BZ, Hou Y, Song F, Lyu HJ, Yue F. Genome-wide detection of enhancer-hijacking events from chromatin interaction data in rearranged genomes. Nat Methods, 2021, 18(6):661-668. |
| [67] | Taberlay PC, Statham AL, Kelly TK, Clark SJ, Jones PA. Reconfiguration of nucleosome-depleted regions at distal regulatory elements accompanies DNA methylation of enhancers and insulators in cancer. Genome Res, 2014, 24(9):1421-1432. |
| [68] | Xiong L, Wu F, Wu Q, Xu LL, Cheung OK, Kang W, Mok MT, Szeto LLM, Lun CY, Lung RW, Zhang JL, Yu KH, Lee S D, Huang GC, Wang CM, Liu J, Yu Z, Yu DY, Chou JL, Huang WH, Feng B, Cheung YS, Lai PB, Tan P, Wong N, Chan MW, Huang TH, Yip KY, Cheng AS, To KF. Aberrant enhancer hypomethylation contributes to hepatic carcinogenesis through global transcriptional reprogramming. Nat Commun, 2019, 10(1):335. |
| [69] | Aran D, Sabato S, Hellman A. DNA methylation of distal regulatory sites characterizes dysregulation of cancer genes. Genome Biol, 2013; 14(3):R21. |
| [70] | Magnani L, Stoeck A, Zhang XY, Lánczky A, Mirabella AC, Wang TL, Gyorffy B, Lupien M. Genome-wide reprogramming of the chromatin landscape underlies endocrine therapy resistance in breast cancer. Proc Natl Acad Sci USA, 2013, 110(16):E1490-E1499. |
| [71] | Wu SH, Turner KM, Nguyen N, Raviram R, Erb M, Santini J, Luebeck J, Rajkumar U, Diao Y, Li B, Zhang WJ, Jameson N, Corces MR, Granja JM, Chen XQ, Coruh C, Abnousi A, Houston J, Ye Z, Hu R, Yu M, Kim H, Law JA, Verhaak RGW, Hu M, Furnari FB, Chang HY, Ren B, Bafna V, Mischel PS. Circular ecDNA promotes accessible chromatin and high oncogene expression. Nature, 2019, 575(7784):699-703. |
| [72] | Morton AR, Dogan-Artun N, Faber ZJ, MacLeod G, Bartels CF, Piazza MS, Allan KC, Mack SC, Wang XX, Gimple RC, Wu QL, Rubin BP, Shetty S, Angers S, Dirks PB, Sallari RC, Lupien M, Rich JN, Scacheri PC. Functional enhancers shape extrachromosomal oncogene amplifications. Cell, 2019, 179(6):1330-1341. |
| [73] | Hung KL, Yost KE, Xie LQ, Shi QM, Helmsauer K, Luebeck J, Schöpflin R, Lange JT, Chamorro González R, Weiser NE, Chen CL, Valieva ME, Wong IT-L, Wu SH, Dehkordi SR, Duffy CV., Kraft K, Tang J, Belk JA, Rose JC, Corces MR, Granja JM, Li R, Rajkumar U, Friedlein J, Bagchi A, Satpathy AT, Tjian R, Mundlos S, Bafna V, Henssen AG, Mischel PS, Liu Z, Chang HY. ecDNA hubs drive cooperative intermolecular oncogene expression. Nature, 2021, 600(7890):731-736. |
| [74] | Herz HM. Enhancer deregulation in cancer and other diseases. Bioessays, 2016, 38(10):1003-1015. |
| [75] | Wu ZQ, Mi ZY. Research progress of super enhancer in cancer. Hereditas(Beijing), 2019, 41(1):41-51. |
| [75] | 吴志强, 米泽云. 超级增强子在肿瘤研究中的进展. 遗传, 2019, 41(1):41-51. |
| [76] | Glodzik D, Morganella S, Davies H, Simpson PT, Li YL, Zou XQ, Diez-Perez J, Staaf J, Alexandrov LB, Smid M, Brinkman AB, Rye IH, Russnes H, Raine K, Purdie CA, Lakhani SR, Thompson AM, Birney E, Stunnenberg HG, van de Vijver MJ, Martens JWM, Børresen-Dale AL, Richardson AL, Kong G, Viari A, Easton D, Evan G, Campbell PJ, Stratton MR, Nik-Zainal S. Corrigendum: a somatic-mutational process recurrently duplicates germline susceptibility loci and tissue-specific super-enhancers in breast cancers. Nat Genet, 2017, 49(3):341-348. |
| [77] | Gu XL, Wang LX, Boldrup L, Coates PJ, Fahraeus R, Sgaramella N, Wilms T, Nylander K. Ap001056.1, a prognosis-related enhancer rna in squamous cell carcinoma of the head and neck. Cancers (Basel), 2019, 11(3):347. |
| [78] | Lee JH, Xiong F, Li WB. Enhancer RNAs in cancer: regulation, mechanisms and therapeutic potential. RNA Biol, 2020, 17(11):1550-1559. |
| [79] | Corces MR, Granja JM, Shams S, Louie BH, Seoane JA, Zhou WD, Silva TC, Groeneveld C, Wong CK, Cho SW, Satpathy AT, Mumbach MR, Hoadley KA, Robertson AG, Sheffield NC, Felau I, Castro MAA, Berman BP, Staudt LM, Zenklusen JC, Laird PW, Curtis C, Greenleaf WJ, Chang HY. The chromatin accessibility landscape of primary human cancers. Science, 2018, 362(6413): eaav1898. |
| [80] | Ding MT, Zhan HJ, Liao XH, Li AL, Zhong YC, Gao QJ, Liu YC, Huang WR, Cai ZM. Enhancer RNA - P2RY2e induced by estrogen promotes malignant behaviors of bladder cancer. Int J Biol Sci, 2018, 14(10):1268-1276. |
| [81] | Hsieh CL, Fei T, Chen YW, Li TT, Gao YF, Wang XD, Sun T, Sweeney CJ, Lee GSM, Chen SY, Balk SP, Liu XS, Brown M, Kantoff PW. Enhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activation. Proc Natl Acad Sci USA, 2014, 111(20):7319-7324. |
| [82] | O’Connor D, Sibson K, Caswell M, Connor P, Cummins M, Mitchell C, Motwani J, Taj M, Vora A, Wynn R, Kearns PR. Early UK experience in the use of clofarabine in the treatment of relapsed and refractory paediatric acute lymphoblastic leukaemia. Br J Haematol, 2011, 154(4):482-485. |
| [83] | Castells M, Thibault B, Delord JP, Couderc B. Implication of tumor microenvironment in chemoresistance: tumor- associated stromal cells protect tumor cells from cell death. Int J Mol Sci, 2012, 13(8):9545-9571. |
| [84] | Rivera E, Gomez H. Chemotherapy resistance in metastatic breast cancer: the evolving role of ixabepilone. Breast Cancer Res, 2010, 12(Suppl 2):S2. |
| [85] | Zhao Y, Wang LG, Ren SC, Wang L, Blackburn PR, McNulty MS, Gao X, Qiao M, Vessella RL, Kohli M, Zhang J, Karnes RJ, Tindall DJ, Kim Y, MacLeod R, Ekker SC, Kang T, Sun YH, Huang HJ. Activation of P-TEFb by androgen receptor-regulated enhancer RNAs in castration-resistant prostate cancer. Cell Rep, 2016, 15(3):599-610. |
/
| 〈 |
|
〉 |