SREBP2 contributes to cisplatin resistance in ovarian cancer cells
Open accessAbstract
This study is to investigate transcription factors involved in cisplatin resistance in ovarian cancer cells. The transcriptome of cisplatin resistant and sensitive A2780 epithelial ovarian cancer cells was obtained from GSE15372. Ovarian transcriptome data GSE62944 was downloaded from TCGA and applied for transcription regulatory network analysis. The analysis results were confirmed using quantitative polymerase chain reaction. The roles of SREBP2 in cisplatin-resistant cells were investigated by RNA inference and cell viability analysis. Transcription regulatory network analysis found that 12 transcription factors and their targets were involved in cisplatin resistant in A2780 cells. Among these factors, the targets of EZH2 and SREBP2 revealed by Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining were also enriched in differentially expressed genes between cisplatin resistant and cisplatin sensitive cells. Their targets were enriched mainly in cell cycle and cholesterol metabolic process, respectively. Bioinformatic analysis illustrated three known targets of SREBP2, namely LDLR, FDFT1, and HMGCR were increased in A2780-resistant cell lines. Additionally, the three genes and SREBP2 were also elevated in live cells after cisplatin treatment via quantitative polymerase chain reaction. Importantly, RNA inference of SREBP2 in A2780 cell line resulted in a decrease of cell viability after cisplatin treatment. SREBP2 played important roles in cisplatin resistance and cholesterol metabolic process might be a novel target for cancer therapy. Impact statement: Transcriptome of cisplatin resistant and sensitive A2780 epithelial ovarian cancer cells was obtained from GSE15372 and TCGA. Twelve transcription factors and their targets were involved in cisplatin resistant. Among these factors, the targets of EZH2 and SREBP2 revealed by Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining were also enriched in differentially expressed genes. Their targets were enriched mainly in cell cycle and cholesterol metabolic process. Three targets of SREBP2, namely LDLR, FDFT1, and HMGCR were increased in A2780-resistant cell lines and were found elevated in live cells after cisplatin treatment via qPCR. RNAi of SREBP2 in A2780 cell line resulted in a decrease of cell viability after cisplatin treatment. SREBP2 played important roles in cisplatin resistance and might be a novel target for cancer therapy.
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FDFT1 has seldom been studied in cancer research; limited studies addressed FDFT1 in prostate cancer, ovarian cancer, and lung cancer, but there is no information on the function of FDFT1 in CRC.
“Limited studies addressed FDFT1 in prostate cancer35, ovarian cancer46, and lung cancer47, but there is no information on the function of FDFT1 in CRC.”
From RETRACTED ARTICLE: Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression (2020) · cites this paper as [46]
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- Authors
- Zheng, L., Li, L., Lu, Y., Jiang, F., & Yang, X.-A.
- Affiliations
- Beijing Scientific Operation Co., Ltd, Beijing 100121, P.R. China
- Peking University International Hospital (CN)
- Department of Nephrology, Affiliated Hospital of Hebei University of Engineering, Handan 056002, P.R. China
- Fifth Affiliated Hospital of Sun Yat-sen University (CN)
- Corresponding author
- Jiang, Fangfang
- Yang, Xiu-An
- Venue
- Experimental Biology and Medicine
- Publisher
- Frontiers Media SA
- Published
- 2018-02-22
- Volume
- 243
- Issue
- 7
- Pages
- 655-662
- ISSN
- 0071-3384 (ISSN-L)
- 1535-3702
- 1535-3699
- PMC
- PMC6582395
- OpenAlex
- W2808027013
- Cited by
- 59
- References
- 38
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 5 · 2023: 3 · 2022: 9 · 2021: 15 · 2020: 10 · 2019: 2 · 2018: 1 · 2017: 1
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Experimental Biology and Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chinese Academy of Sciences
- Peking University
- Institute of Biophysics, Chinese Academy of Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- SREBP2, cisplatin resistance, ovarian cancer, A2780 cells, transcriptional regulatory networks, EZH2, cholesterol metabolism, LDL receptor, FDFT1, HMGCR, cell cycle, transcription factors, cell viability
- MeSH terms
- Cell Survival, Cisplatin, Female, Humans, Ovarian Neoplasms, Ovary, Transcription, Genetic, Gene Expression Regulation, Neoplastic, Drug Resistance, Neoplasm, RNA Interference, Cell Line, Tumor, Sterol Regulatory Element Binding Protein 2, Transcriptome
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