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Transcriptomics profiling of breast cancer cells, MDA‐MB‐231, exposed to TNF‐α: focus on pro‐survival and pro‐inflammatory regulated pathways.
Author(s) -
Bauer David F.,
Mazzio Elizabeth A.,
Soliman Karam F.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.39.3
Subject(s) - proinflammatory cytokine , tumor necrosis factor alpha , cancer research , breast cancer , transcriptome , chemokine , downregulation and upregulation , tumor microenvironment , inflammation , biology , medicine , immunology , cancer , gene expression , genetics , gene , tumor cells
Triple‐negative breast cancer (TNBC) is characterized by the absence of estrogen, progesterone and HER2 receptors. TNBC is considered to have a poor prognosis due to the limited treatment options with the exclusion of hormone receptor‐based chemotherapies. Aggressive TNBC growth is accompanied by infiltration of tumor‐associated macrophages which can establish a perpetual state of inflammation rendering sustained release of proinflammatory cytokines such as tumor necrosis factor (TNF)‐α, which can lead to immunological evasion. In this work, we evaluated the effects of TNF‐α on the changes to the whole transcriptome: including mRNAs, long intergenic non‐coding RNA transcripts (lincRNA) in MDA‐MB‐231 cells. The data show enormous upregulation (60‐fold change FC, p<.0001) in CXCL8 chemokine (C‐X‐C motif) ligand 8, with a statistically significant elevation of other transcripts including IL‐6 (+10.47), TNFRSF9 (9.58), TNFAIP3 (+7.52) and CCL2 (+3.5). On the other side, there was a reduction in numerous non‐coding microRNA including MIR29A (−8.8), MIRLET7A2 (−8.7), MIR222 (−4.91), MIR100 (−4.91), MIR27B (−4.68) and MIR181B1 (−7.95) in addition to Glutathione S – transferase (GSTT2) (−5.59). Pathway analysis shows that the most relevant effects of TNF‐α are on driving NF‐kB related survival, cytokines, and inflammatory pathway elements and TNF‐α related pathways. Support or Funding Information Supported by grants from the National Institute on Minority Health and Health Disparities RCMI grant G12MD007582 and COE grant P20 MD006738. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .