Thymoquinone upregulates IL17RD in controlling the growth and metastasis of triple negative breast cancer cells in vitro

Background Triple negative breast cancer (TNBC) is a molecular subtype of breast cancer, which is a major health burden of females worldwide. Thymoquinone (TQ), a natural compound, has been found to be effective against TNBC cells, and this study identified IL17RD as a novel target of TQ in TNBC cel...

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Published in:BMC cancer 2022-06, Vol.22 (1), p.1-707, Article 707
Main Authors: Khan, Md. Asaduzzaman, Zheng, Meiling, Fu, Jiewen, Tania, Mousumi, Li, Jun, Fu, Junjiang
Format: Article
Language:English
Subjects:
Analysis
Antibodies
Antimitotic agents
Antineoplastic agents
Breast cancer
Cancer cells
Cancer therapies
Cell culture
Chemotherapy
ChIP-Seq
Chromatin
Comparative analysis
Composition
DNA methylation
Dosage and administration
Epigenetic inheritance
Epigenetics
FDA approval
Genomes
IL17RD
Immunoprecipitation
Infrared imaging systems
Medical research
Mehtylation
Metastases
Metastasis
Phytochemicals
Prevention
Proteins
Risk factors
Thymoquinone
Triple negative breast cancer
Tumor suppressor genes
Tumors
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Summary:Background Triple negative breast cancer (TNBC) is a molecular subtype of breast cancer, which is a major health burden of females worldwide. Thymoquinone (TQ), a natural compound, has been found to be effective against TNBC cells, and this study identified IL17RD as a novel target of TQ in TNBC cells. Methods We have performed chromatin immunoprecipitation Sequence (ChIP-Seq) by MBD1 (methyl-CpG binding domain protein 1) antibody to identify genome-wide methylated sites affected by TQ. ChIP-seq identified 136 genes, including the tumor suppressor IL17RD, as a novel target of TQ, which is epigenetically upregulated by TQ in TNBC cell lines BT-549 and MDA-MB-231. The IL17RD expression and survival outcomes were studied by Kaplan-Meier analysis. Results TQ treatment inhibited the growth, migration, and invasion of TNBC cells with or without IL17RD overexpression or knockdown, while the combination of IL17RD overexpression and TQ treatment were the most effective against TNBC cells. Moreover, higher expression of IL17RD is associated with longer survival in TNBC patients, indicating potential therapeutic roles of TQ and IL17RD against TNBC. Conclusions Our data suggest that IL17RD might be epigenetically upregulated in TNBC cell lines by TQ, and this might be one of the mechanisms by which TQ exerts its anticancer and antimetastatic effects on TNBC cells. Keywords: Triple negative breast cancer, Epigenetics, Thymoquinone, ChIP-Seq, Mehtylation, IL17RD
ISSN:1471-2407
1471-2407
DOI:10.1186/s12885-022-09782-z