Generic placeholder image

当代肿瘤药物靶点

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Research Article

Linc01638促进HER 2乳腺癌的肿瘤发生

卷 19, 期 1, 2019

页: [74 - 80] 页: 7

弟呕挨: 10.2174/1568009618666180709163718

open access plus

conference banner
摘要

背景:长时间的非编码RNA在各种生物活动和疾病中起着至关重要的作用.长基因间非编码RNA 01638(Linc 01638)在乳腺癌特别是HER2-pos中的作用乳癌,很大程度上仍不为人所知。 目的:探讨linc 01638在HER 2阳性乳腺癌发生中的作用。 方法:首先应用qRT-PCR技术检测HER 2阳性乳腺癌细胞和组织中linc 01638的表达。然后分析linc 01638在HER 2阳性乳腺癌细胞中的表达情况。LS通过细胞凋亡试验、细胞增殖试验、集落形成试验和细胞侵袭试验。我们建立小鼠异种移植模型,进一步证实linc 01638在her 2阳性中的作用。乳腺癌此外,我们还用Western blot和IHC分析了linc 01638对移植瘤中Dnmts、BRCA 1和PTEN表达的影响。 结果:Linc01638在HER 2阳性乳腺癌细胞和组织中表达明显增高。抑制linc 01638促进细胞凋亡,抑制细胞生长和抑制invHER 2阳性乳腺癌细胞体外活性与体内肿瘤进展和转移的关系。此外,shRNA对linc 01638的抑制作用还减弱了DNMT 1、DNMT3a和Dnmt3b的表达,促进HER 2阳性乳腺癌细胞和小鼠移植瘤细胞BRCA 1和PTEN的表达。 结论:Linc01638有可能成为治疗HER 2阳性乳腺癌的重要生物标志物和治疗靶点。

关键词: 长非编码RNA,Linc01638,Dnmts,HER 2阳性乳腺癌,肿瘤发生。

« Previous
[1]
Torre, L.A.; Bray, F.; Siegel, R.L.; Ferlay, J.; Lortet-Tieulent, J.; Jemal, A. Global cancer statistics, 2012. CA Cancer J. Clin., 2015, 65(2), 87-108.
[2]
Figueroa-Magalhaes, M.C.; Jelovac, D.; Connolly, R.; Wolff, A.C. Treatment of HER2-positive breast cancer. Breast, 2014, 23(2), 128-136.
[3]
Prat, A.; Pineda, E.; Adamo, B.; Galván, P.; Fernández, A.; Gaba, L.; Díez, M.; Viladot, M.; Arance, A.; Muñoz, M. Clinical implications of the intrinsic molecular subtypes of breast cancer. Breast, 2015, 24(Suppl. 2), S26-S35.
[4]
Abramson, V.G.; Lehmann, B.D.; Ballinger, T.J.; Pietenpol, J.A. Subtyping of triple-negative breast cancer: implications for therapy. Cancer, 2015, 121(1), 8-16.
[5]
Carey, L.A.; Perou, C.M.; Livasy, C.A.; Dressler, L.G.; Cowan, D.; Conway, K.; Karaca, G.; Troester, M.A.; Tse, C.K.; Edmiston, S.; Deming, S.L.; Geradts, J.; Cheang, M.C.; Nielsen, T.O.; Moorman, P.G.; Earp, H.S.; Millikan, R.C. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA, 2006, 295(21), 2492-2502.
[6]
Slamon, D.J.; Clark, G.M.; Wong, S.G.; Levin, W.J.; Ullrich, A.; McGuire, W.L. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science, 1987, 235(4785), 177-182.
[7]
Slamon, D.J.; Godolphin, W.; Jones, L.A.; Holt, J.A.; Wong, S.G.; Keith, D.E.; Levin, W.J.; Stuart, S.G.; Udove, J.; Ullrich, A. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science, 1989, 244(4905), 707-712.
[8]
Burstein, H.J. The distinctive nature of HER2-positive breast cancers. N. Engl. J. Med., 2005, 353(16), 1652-1654.
[9]
Ahmed, S.; Sami, A.; Xiang, J. HER2-directed therapy: current treatment options for HER2-positive breast cancer. Breast Cancer, 2015, 22(2), 101-116.
[10]
Slamon, D.J.; Leyland-Jones, B.; Shak, S.; Fuchs, H.; Paton, V.; Bajamonde, A.; Fleming, T.; Eiermann, W.; Wolter, J.; Pegram, M.; Baselga, J. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med., 2001, 344(11), 783-792.
[11]
Berry, D.A.; Cronin, K.A.; Plevritis, S.K.; Fryback, D.G.; Clarke, L.; Zelen, M.; Mandelblatt, J.S.; Yakovlev, A.Y.; Habbema, J.D.F.; Feuer, E.J. Effect of screening and adjuvant therapy on mortality from breast cancer. N. Engl. J. Med., 2005, 353(17), 1784-1792.
[12]
Perez, E.A.; Romond, E.H.; Suman, V.J.; Jeong, J.H.; Sledge, G.; Geyer, Jr, C.E.; Martino, S.; Rastogi, P.; Gralow, J.; Swain, S.M.; Winer, E.P. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J. Clin. Oncol., 2014, 32(33), 3744-3752.
[13]
Kumler, I.; Tuxen, M.K.; Nielsen, D.L. A systematic review of dual targeting in HER2-positive breast cancer. Cancer Treat. Rev., 2014, 40(2), 259-270.
[14]
Nahta, R.; Esteva, F.J. Herceptin: mechanisms of action and resistance. Cancer Lett., 2006, 232(2), 123-138.
[15]
Wapinski, O.; Chang, H.Y. Long noncoding RNAs and human disease. Trends Cell Biol., 2011, 21(6), 354-361.
[16]
Feng, Y.; Hu, X.; Zhang, Y.; Zhang, D.; Li, C.; Zhang, L. Methods for the study of long noncoding RNA in cancer cell signaling. Methods Mol. Biol., 2014, 1165, 115-143.
[17]
Hauptman, N.; Glavac, D. Long non-coding RNA in cancer. Int. J. Mol. Sci., 2013, 14(3), 4655-4669.
[18]
Faghihi, M.A.; Modarresi, F.; Khalil, A.M.; Wood, D.E.; Sahagan, B.G.; Morgan, T.E.; Finch, C.E.; Laurent, III, G.S.; Kenny, P.J.; Wahlestedt, C. Expression of a noncoding RNA is elevated in Alzheimer’s disease and drives rapid feed-forward regulation of beta-secretase. Nat. Med., 2008, 14(7), 723-730.
[19]
McPherson, R.; Pertsemlidis, A.; Kavaslar, N.; Stewart, A.; Roberts, R.; Cox, D.R.; Hinds, D.A.; Pennacchio, L.A.; Tybjaerg-Hansen, A.; Folsom, A.R.; Boerwinkle, E. A common allele on chromosome 9 associated with coronary heart disease. Science, 2007, 316(5830), 1488-1491.
[20]
Sigdel, K.R.; Cheng, A.; Wang, Y.; Duan, L.; Zhang, Y. The emerging functions of long noncoding RNA in immune cells: autoimmune diseases. J. Immunol. Res., 2015, 2015, 848790.
[21]
Yang, X.; Xie, X.; Xiao, Y.F.; Xie, R.; Hu, C.J.; Tang, B.; Li, B.S.; Yang, S.M. The emergence of long non-coding RNAs in the tumorigenesis of hepatocellular carcinoma. Cancer Lett., 2015, 360(2), 119-124.
[22]
Shao, Y.; Ye, M.; Jiang, X.; Sun, W.; Ding, X.; Liu, Z.; Ye, G.; Zhang, X.; Xiao, B.; Guo, J. Gastric juice long noncoding RNA used as a tumor marker for screening gastric cancer. Cancer, 2014, 120(21), 3320-3328.
[23]
Wang, L.; Fu, D.; Qiu, Y.; Xing, X.; Xu, F.; Han, C.; Xu, X.; Wei, Z.; Zhang, Z.; Ge, J.; Cheng, W. Genome-wide screening and identification of long noncoding RNAs and their interaction with protein coding RNAs in bladder urothelial cell carcinoma. Cancer Lett., 2014, 349(1), 77-86.
[24]
Peter, S.; Borkowska, E.; Drayton, R.M.; Rakhit, C.P.; Noon, A.P.; Chen, W.; Catto, J.W. Identification of differentially expressed long noncoding RNAs in bladder cancer. Clin. Cancer Res., 2014, 20(20), 5311-5321.
[25]
Hirata, H.; Hinoda, Y.; Shahryari, V.; Deng, G.; Nakajima, K.; Tabatabai, Z.L.; Ishii, N.; Dahiya, R. Long noncoding RNA MALAT1 promotes aggressive renal cell carcinoma through Ezh2 and interacts with miR-205. Cancer Res., 2015, 75(7), 1322-1331.
[26]
Wu, J.; Shuang, Z.; Zhao, J.; Tang, H.; Liu, P.; Zhang, L.; Xie, X.; Xiao, X. Linc00152 promotes tumorigenesis by regulating DNMTs in triple-negative breast cancer. Biomed. Pharmacother., 2018, 97, 1275-1281.
[27]
Tuo, Y.L.; Li, X.M.; Luo, J. Long noncoding RNA UCA1 modulates breast cancer cell growth and apoptosis through decreasing tumor suppressive miR-143. Eur. Rev. Med. Pharmacol. Sci., 2015, 19(18), 3403-3411.
[28]
Sun, M.; Gadad, S.S.; Kim, D.S.; Kraus, W.L. Discovery, annotation, and functional analysis of long noncoding RNAs controlling cell-cycle gene expression and proliferation in breast cancer cells. Mol. Cell, 2015, 59(4), 698-711.
[29]
Luczak, M.W.; Jagodzinski, P.P. The role of DNA methylation in cancer development. Folia Histochem. Cytobiol., 2006, 44(3), 143-154.
[30]
Robertson, K.D. DNA methylation and human disease. Nat. Rev. Genet., 2005, 6(8), 597-610.
[31]
Jin, B.; Robertson, K.D. DNA methyltransferases, DNA damage repair, and cancer. Adv. Exp. Med. Biol., 2013, 754, 3-29.
[32]
Poomipark, N.; Flatley, J.E.; Hill, M.H.; Mangnall, B.; Azar, E.; Grabowski, P. Methyl Donor Status Influences DNMT Expression and Global DNA Methylation in Cervical Cancer Cells. Asian Pac. J. Cancer Prev., 2016, 17(7), 3213-3222.
[33]
Poomipark, N.; Flatley, J.E.; Hill, M.H.; Mangnall, B.; Azar, E.; Grabowski, P.; Powers, H.J. Epigenetics and miRNA as predictive markers and targets for lung cancer chemotherapy. Cancer Biol. Ther., 2015, 16(7), 1056-1070.
[34]
Sun, H.; Wang, G.; Peng, Y.; Zeng, Y.; Zhu, Q.N.; Li, T.L.; Cai, J.Q.; Zhou, H.H.; Zhu, Y.S. H19 lncRNA mediates 17beta-estradiol-induced cell proliferation in MCF-7 breast cancer cells. Oncol. Rep., 2015, 33(6), 3045-3052.
[35]
Hayes, E.L.; Lewis-Wambi, J.S. Mechanisms of endocrine resistance in breast cancer: an overview of the proposed roles of noncoding RNA. Breast Cancer Res., 2015, 17, 40.
[36]
Pickard, M.R.; Williams, G.T. Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: implications for chemotherapy. Breast Cancer Res. Treat., 2014, 145(2), 359-370.
[37]
Liu, Y.; Sharma, S.; Watabe, K. Roles of lncRNA in breast cancer. Front. Biosci., 2015, 7, 94-108.
[38]
Yang, F.; Lyu, S.; Dong, S.; Liu, Y.; Zhang, X.; Wang, O. Expression profile analysis of long noncoding RNA in HER-2-enriched subtype breast cancer by next-generation sequencing and bioinformatics. OncoTargets Ther., 2016, 9, 761-772.
[39]
Denis, H.; Ndlovu, M.N.; Fuks, F. Regulation of mammalian DNA methyltransferases: a route to new mechanisms. EMBO Rep., 2011, 12(7), 647-656.
[40]
Zhou, W.; Jiang, Z.; Liu, N.; Xu, F.; Wen, P.; Liu, Y.; Zhong, W.; Song, X.; Chang, X.; Zhang, X.; Wei, G. Down-regulation of CXCL12 mRNA expression by promoter hypermethylation and its association with metastatic progression in human breast carcinomas. J. Cancer Res. Clin. Oncol., 2009, 135(1), 91-102.
[41]
Dou, S.; Yao, Y.D.; Yang, X.Z.; Sun, T.M.; Mao, C.Q.; Song, E.W.; Wang, J. Anti-Her2 single-chain antibody mediated DNMTs-siRNA delivery for targeted breast cancer therapy. J. Control. Release, 2012, 161(3), 875-883.

© 2024 Bentham Science Publishers | Privacy Policy