Differential Expression and Pathway Analysis in Drug-Resistant Triple-Negative Breast Cancer Cell Lines Using RNASeq Analysis

被引:25
作者
Shaheen, Safa [1 ]
Fawaz, Febin [1 ]
Shah, Shaheen [1 ]
Busselberg, Dietrich [2 ]
机构
[1] Genom Cent, Trichur 680125, India
[2] Qatar Fdn Educ City, Weill Cornell Med, POB 24144, Doha, Qatar
关键词
Triple-negative breast cancer; drug resistance; RNASeq; cytokine-cytokine receptor interaction; basal b; THERAPEUTIC RESISTANCE; SIGNALING PATHWAY; SEQ; BIOLOGY;
D O I
10.3390/ijms19061810
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Triple-negative breast cancer (TNBC) is among the most notorious types of breast cancer, the treatment of which does not give consistent results due to the absence of the three receptors (estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) as well as high amount of molecular variability. Drug resistance also contributes to treatment unresponsiveness. We studied differentially expressed genes, their biological roles, as well as pathways from RNA-Seq datasets of two different TNBC drug-resistant cell lines of Basal B subtype SUM159 and MDA-MB-231 treated with drugs JQ1 and Dexamethasone, respectively, to elucidate the mechanism of drug resistance. RNA sequencing(RNA-Seq) data analysis was done using edgeR which is an efficient program for determining the most significant Differentially Expressed Genes (DEGs), Gene Ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. iPathway analysis was further used to obtain validated results using analysis that takes into consideration type, function, and interactions of genes in the pathway. The significant similarities and differences throw light into the molecular heterogeneity of TNBC, giving clues into the aspects that can be focused to overcome drug resistance. From this study, cytokine-cytokine receptor interaction pathway appeared to be a key factor in TNBC drug resistance.
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页数:13
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共 33 条
[1]   ADAMTSL5 and CDH11: putative epigenetic markers for therapeutic resistance in acute lymphoblastic leukemia [J].
Abdullah, Maha ;
Choo, Chee Wei ;
Alias, Hamidah ;
Rahman, Eni Juraidah Abdul ;
Ibrahim, Hishamshah Mohd ;
Jamal, Rahman ;
Hussin, Noor Hamidah .
HEMATOLOGY, 2017, 22 (07) :386-391
[2]   Triple Negative Breast Cancer: A Tale of Two Decades [J].
Ali, Arwa M. ;
Ansari, Jawaher A. K. ;
Abd El-Aziz, Nashwa M. ;
Abozeed, Waleed N. ;
Warith, Ahmed M. Abdel ;
Alsaleh, Khalid ;
Nabholtz, Jean-Marc .
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 2017, 17 (04) :491-499
[3]   Cadherins as novel targets for anti-cancer therapy [J].
Blaschuk, Orest W. ;
Devemy, Emmanuelle .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2009, 625 (1-3) :195-198
[4]   Combined drug therapeutic strategies for the effective treatment of Triple Negative Breast Cancer [J].
Chalakur-Ramireddy, Naveen K. R. ;
Pakala, Suresh B. .
BIOSCIENCE REPORTS, 2018, 38
[5]  
Chavez Kathryn J, 2010, Breast Dis, V32, P35, DOI 10.3233/BD-2010-0307
[6]   Leveraging Big Data to Transform Target Selection and Drug Discovery [J].
Chen, B. ;
Butte, A. J. .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2016, 99 (03) :285-297
[7]  
Chen Yunshun, 2016, F1000Res, V5, P1438, DOI 10.12688/f1000research.8987.2
[8]   Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer [J].
Chen, Zhong ;
Lan, Xun ;
Wu, Dayong ;
Sunkel, Benjamin ;
Ye, Zhenqing ;
Huang, Jiaoti ;
Liu, Zhihua ;
Clinton, Steven K. ;
Jin, Victor X. ;
Wang, Qianben .
NATURE COMMUNICATIONS, 2015, 6
[9]   The SLC37 Family of Sugar-Phosphate/Phosphate Exchangers [J].
Chou, Janice Y. ;
Mansfield, Brian C. .
EXCHANGERS, 2014, 73 :357-382
[10]   Targeting the PI3K/AKT/mTOR pathway in triple-negative breast cancer: a review [J].
Costa, Ricardo L. B. ;
Han, Hyo Sook ;
Gradishar, William J. .
BREAST CANCER RESEARCH AND TREATMENT, 2018, 169 (03) :397-406