The long non-coding RNA ADAMTS9-AS2 was identified as a potential prognostic biomarker in triple-negative breast cancer / O RNA longo não codificador ADAMTS9-AS2 foi identificado como um potencial biomarcador prognóstico no câncer de mama triplo negativo
DOI:
https://doi.org/10.34117/bjdv6n3-479Keywords:
lncRNA, breast cancer, biomarker, TNBC.Abstract
Introdução: O câncer de mama é a principal causa de mortes relacionadas ao câncer em mulheres no Brasil e no mundo. O subtipo de câncer de mama triplo negativo (TNBC) é uma doença complexa, com prognóstico ruim e opções terapêuticas limitadas, sendo a quimioterapia a base do tratamento para as pacientes. Uma variedade de RNA longo não codificante foi associada à progressão tumoral e à quimiorresistência no câncer de mama. Objetivo: O objetivo deste estudo foi identificar um potencial biomarcador prognóstico em pacientes com TNBC. Métodos: Um conjunto de dados de microarranjos contendo assinaturas de expressão de 165 TNBC (GSE76250) foi avaliado e uma análise in silico foi realizada para identificar novos possíveis biomarcadores no TNBC. Resultados:ADAMTS9-S2 foi a transcrição mais significativa identificada pelas ferramentas GEO2R. Baixos níveis de ADAMTS9-S2 foram observados em receptores hormonais negativos (p <0,0001) e alta expressão em pacientes com HER2 negativo (p <0,0001). Em nosso estudo, a baixa expressão de ADAMTS9-S2 foi associada à baixa sobrevida livre de recidiva em pacientes com TNBC. Conclusão: Nosso estudo fornece evidências de que o ADAMTS9-S2 pode ser um potencial biomarcador prognóstico em pacientes com TNBC. No entanto, mais estudos funcionais são necessários para entender, caracterizar e confirmar os padrões de expressão do ADAMTS9-AS2 e a relação com a progressão do TNBC.
References
Werutsky G, Nunes P, Barrios C. Locally advanced breast cancer in Brazil: Current status and future perspectives. Ecancermedicalscience. 2019 Jan 22;13.
McDonald KA, Kawaguchi T, Qi Q, Peng X, Asaoka M, Young J, et al. Tumor Heterogeneity Correlates with Less Immune Response and Worse Survival in Breast Cancer Patients. Ann Surg Oncol. 2019 Jul 15;26(7):2191–9.
Aysola K, Desai A, Welch C, Xu J, Qin Y, Reddy V, et al. Triple Negative Breast Cancer-An Overview. Hered Genet. 2013;2013(2).
Collignon J, Lousberg L, Schroeder H, Jerusalem G. Triple-negative breast cancer: treatment challenges and solutions. 2016 [cited 2020 Jan 13]; Available from: http://dx.doi.org/10.2147/BCTT.S69488
Qi M, Yu B, Yu H, Li F. Integrated analysis of a ceRNA network reveals potential prognostic lncRNAs in gastric cancer. Cancer Med [Internet]. 2020 Jan 10 [cited 2020 Jan 13];cam4.2760. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/cam4.2760
Shi X, Zhang W, Nian X, Lu X, Li Y, Liu F, et al. The previously uncharacterized lncRNA APP promotes prostate cancer progression by acting as a competing endogenous RNA. Int J Cancer. 2019;
Wang L, Meng D, Wang Y, Hu J. Long non-coding RNA LINC01296 promotes esophageal squamous cell carcinoma cell proliferation and invasion by epigenetic suppression of KLF2. Am J Cancer Res [Internet]. 2018 [cited 2020 Jan 13];8(10):2020–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30416853
Yang Y, Chen Q, Piao H, Wang B, Zhu G, Chen E, et al. HNRNPAB?regulated lncRNA?ELF209 inhibits the malignancy of hepatocellular carcinoma. Int J Cancer [Internet]. 2020 Jan 17 [cited 2020 Jan 13];146(1):169–80. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.32409
Liu L, Zhan Y, Huang Y, Huang L. LncRNA FGD5?AS1 can be predicted as therapeutic target in oral cancer. J Oral Pathol Med [Internet]. 2020 Jan 3 [cited 2020 Jan 13];jop.12989. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/jop.12989
Cui Y, Lu C, Zhang Z, Mao A, Feng L, Fu L, et al. A Long Non-coding RNA Lnc712 Regulates Breast Cancer Cell Proliferation. Int J Biol Sci [Internet]. 2020 [cited 2020 Jan 13];16(1):162–71. Available from: http://www.ijbs.com/v16p0162.htm
Giro-Perafita A, Luo L, Khodadadi-Jamayran A, Thompson M, Akgol Oksuz B, Tsirigos A, et al. LncRNA RP11-19E11 is an E2F1 target required for proliferation and survival of basal breast cancer. npj Breast Cancer [Internet]. 2020 Dec 6 [cited 2020 Jan 13];6(1):1. Available from: http://www.nature.com/articles/s41523-019-0144-4
Dahariya S, Paddibhatla I, Kumar S, Raghuwanshi S, Pallepati A, Gutti RK. Long non-coding RNA: Classification, biogenesis and functions in blood cells. Vol. 112, Molecular Immunology. Elsevier Ltd; 2019. p. 82–92.
Jarroux J, Morillon A, Pinskaya M. History, discovery, and classification of lncRNAs. In: Advances in Experimental Medicine and Biology. Springer New York LLC; 2017. p. 1–46.
Wang J, Sun J, Yang F. The role of long non coding RNA H19 in breast cancer (Review). Oncol Lett. 2020;19(1):7–16.
Wang J, Xie S, Yang J, Xiong H, Jia Y, Zhou Y, et al. The long noncoding RNA H19 promotes tamoxifen resistance in breast cancer via autophagy. J Hematol Oncol [Internet]. 2019 Dec 24 [cited 2020 Jan 13];12(1):81. Available from: https://jhoonline.biomedcentral.com/articles/10.1186/s13045-019-0747-0
Paw?owska E, Szczepanska J, Blasiak J. The long noncoding RNA HOTAIR in breast cancer: Does autophagy play a role? Int J Mol Sci [Internet]. 2017 [cited 2020 Jan 13];18(11). Available from: http://www.genecards.org/cgi-bin/carddisp.pl?gene=HOTAIR;
Song EL, Xing L, Wang L, Song WT, Li D Bin, Wang Y, et al. LncRNA ADAMTS9-AS2 inhibits cell proliferation and decreases chemoresistance in clear cell renal cell carcinoma via the miR-27a-3p/FOXO1 axis. Aging (Albany NY). 2019 Aug 15;11(15):5705–25.
Li Y, Wan Q, Wang W, Mai L, Sha L, Mashrah M, et al. LncRNA ADAMTS9-AS2 promotes tongue squamous cell carcinoma proliferation, migration and EMT via the miR-600/EZH2 axis. Biomed Pharmacother. 2019 Apr 1;112.
Jiang YZ, Liu YR, Xu XE, Jin X, Hu X, Yu K Da, et al. Transcriptome Analysis of Triple-Negative Breast Cancer Reveals an Integrated mRNA-lncRNA Signature with Predictive and Prognostic Value. Vol. 76, Cancer Research. American Association for Cancer Research Inc.; 2016. p. 2105–14.
GTEx Project. GTEx portal. GTEx Analysis Release V6p (dbGaP Accession phs000424.v6.p1). 2017.
Shao B, Feng Y, Zhang H, Yu F, Li Q, Tan C, et al. The 3p14.2 tumour suppressor ADAMTS9 is inactivated by promoter CpG methylation and inhibits tumour cell growth in breast cancer. J Cell Mol Med. 2018 Feb 1;22(2):1257–71.
Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011 Jul;121(7):2750–67.
Santonja A, Sánchez-Muñoz A, Lluch A, Chica-Parrado MR, Albanell J, Chacón JI, et al. Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy. Oncotarget. 2018 May 29;9(41):26406–16.
Deva Magendhra Rao AK, Patel K, Korivi Jyothiraj S, Meenakumari B, Sundersingh S, Sridevi V, et al. Identification of lncRNAs associated with early-stage breast cancer and their prognostic implications. Mol Oncol. 2019 Jun 1;13(6):1342–55.
Yao J, Zhou B, Zhang J, Geng P, Liu K, Zhu Y, et al. A new tumor suppressor LncRNA ADAMTS9-AS2 is regulated by DNMT1 and inhibits migration of glioma cells. Tumor Biol [Internet]. 2014 Aug 15;35(8):7935–44. Available from: http://link.springer.com/10.1007/s13277-014-1949-2
Shi YF, Lu H, Wang HB. Downregulated lncRNA ADAMTS9-AS2 in breast cancer enhances tamoxifen resistance by activating microRNA-130a-5p. Eur Rev Med Pharmacol Sci. 2019;23(4):1563–73.
Ho H, Aruri J, Kapadia R, Mehr H, White MA, Ganesan AK. RhoJ regulates melanoma chemoresistance by suppressing pathways that sense DNA damage. Cancer Res [Internet]. 2012 Nov 1;72(21):5516–28. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22971344
Wang H, Schaefer T, Konantz M, Braun M, Varga Z, Paczulla AM, et al. Prominent Oncogenic Roles of EVI1 in Breast Carcinoma. Cancer Res [Internet]. 2017;77(8):2148–60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28209621
Zeng T, Chen C, Yang P, Zuo W, Liu X, Zhang Y. A Protective Role for RHOJ in NonSmall Cell Lung Cancer Based on Integrated Bioinformatics Analysis. J Comput Biol [Internet]. 2019 Oct 23; Available from: http://www.ncbi.nlm.nih.gov/pubmed/31638412
Liu YR, Jiang YZ, Xu XE, Hu X, Yu K Da, Shao ZM. Comprehensive transcriptome profiling reveals multigene signatures in triple-negative breast cancer. Clin Cancer Res. 2016 Apr 1;22(7):1653–62.
