C/EBPβ enhances platinum resistance of ovarian cancer cells by reprogramming H3K79 methylation

Liu, Dan; Zhang, Xiaoxue; Li, Mengchen; Cao, Canhui; Wan, Dongyi; Xi, Bixin; Tan, Jiahong; Ji, Wang; Yang, Zongyuan; Feng, Xiang; Ye, Fei; Chen, Gang; Wu, Peng; Liu, Xi; Wang, Hui; Zhou, Jianfeng; Feng, Zuo-Hua; Ma, Ding; Gao, Qinglei

doi:10.1038/s41467-018-03590-5

Cited by 95 publications

(86 citation statements)

References 70 publications

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“…59,60 In Ewing sarcoma and ovarian cancer, CEBPB could promote tumor cell resistance to chemotherapy. 61,62 In this study, we found that CEBPB promotes the transcription of CPT1A and activates FAO. We confirmed that PGC1α binds to CEBPB and is co-localized to the promoter of CPT1A; knockdown of CEBPB sensitized NPC cells to radiation therapy.…”

Section: Discussionsupporting

confidence: 51%

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PGC1α/CEBPB/CPT1A axis promotes radiation resistance of nasopharyngeal carcinoma through activating fatty acid oxidation

Tan

Shi

et al. 2019

Cancer Science

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The PPAR coactivator‐1α (PGC1α) is an important transcriptional co‐activator in control of fatty acid metabolism. Mitochondrial fatty acid oxidation (FAO) is the primary pathway for the degradation of fatty acids and promotes NADPH and ATP production. Our previous study demonstrated that upregulation of carnitine palmitoyl transferase 1 A (CPT1A), the key regulator of FAO, promotes radiation resistance of nasopharyngeal carcinoma (NPC). In this study, we found that high expression of PGC1α is associated with poor overall survival in NPC patients after radiation treatment. Targeting PGC1α could sensitize NPC cells to radiotherapy. Mechanically, PGC1α binds to CCAAT/enhancer binding protein β (CEBPB), a member of the transcription factor family of CEBP, to promote CPT1A transcription, resulting in activation of FAO. Our results revealed that the PGC1α/CEBPB/CPT1A/FAO signaling axis promotes radiation resistance of NPC. These findings indicate that the expression of PGC1α could be a prognostic indicator of NPC, and targeting FAO in NPC with high expression of PGC1α might improve the therapeutic efficacy of radiotherapy.

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Section: Discussionsupporting

confidence: 51%

“…CEBPB expression is associated with overall survival in breast cancer and gastric cancer patients . In Ewing sarcoma and ovarian cancer, CEBPB could promote tumor cell resistance to chemotherapy . In this study, we found that CEBPB promotes the transcription of CPT1A and activates FAO.…”

Section: Discussionmentioning

confidence: 51%

PGC1α/CEBPB/CPT1A axis promotes radiation resistance of nasopharyngeal carcinoma through activating fatty acid oxidation

Tan

Shi

et al. 2019

Cancer Science

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“…every other day for three times. 28,29 Tumor volumes were estimated (volume = length • width 2 • 0.52) every 4 days until tumor volume reached 2,500-3,000 mm 3 or tumor ulceration occurred. Six weeks after tumor cell inoculation (day [D] 42), mice were killed and tumor tissues were dissected immediately after death.…”

Section: In Vivo Animal Studiesmentioning

confidence: 99%

Truncated Bid Regulates Cisplatin Response via Activation of Mitochondrial Apoptosis Pathway in Ovarian Cancer

Dai

Zhao

et al. 2020

Human Gene Therapy

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Refractoriness to conventional chemotherapy is a major challenge in the treatment of advanced ovarian cancer (OC). There is increasing evidence that mitochondrial priming correlates with cisplatin response in various cancers. Notably, Bim and Bid, two of the proapoptotic BH3-only proteins, are recognized as the most effective inducers of mitochondrial priming in OC. In this study, we constructed two tumor-specific oncolytic adenoviruses (Ads) coding for Bim (Ad-Bim) or truncated Bid (Ad-tBid), respectively, and performed gain-of-function assays in nine OC cell lines. Ad-tBid exhibited significant antitumor efficacy than the controls. On addition of Ad-tBid pretreatment, mito-primed cells displayed more sensitivity to cisplatin both in vitro and ex vivo. We also found that Ad-tBid induced mitochondrial apoptosis in a Bakdependent manner. Furthermore, a combined cisplatin plus Ad-tBid therapy markedly inhibited tumor growth in a subcutaneous xenotransplanted tumor model. In mice bearing peritoneal disseminated OC, intraperitoneal administration of Ad-tBid potentiated the antitumor effect of cisplatin. Our findings suggest that Ad-tBid enhances cisplatin response in OC cells, establishing the potential treatment of advanced OC via a combination of cisplatin and Ad-tBid.

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“…Presence of two or more methylated genes in patients significantly correlated with disease recurrence (hazard ratio: 1.91; p = 0.002) and shorter overall survival and disease free survival (hazard ratio: 1.96; p = 0.006) (Lin et al, 2018). Liu et al reported the prognostic potential of C/EBPβ (a transcription factor) which augments chemoresistance of ovarian cancer cells by maintaining an open chromatin state via reprogramming H3K79 methylation of multiple drug-resistance genes upon direct interaction with DOT1L (DNA methyltransferase), thus provides a new insight for more precise therapeutics options in OC by identifying and targeting the key regulators of epigenetics (Liu et al, 2018).…”

Section: Prognosismentioning

confidence: 99%

Epigenetic Biomarkers in the Management of Ovarian Cancer: Current Prospectives

Singh

Gupta

Sachan

2019

Front. Cell Dev. Biol.

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Ovarian cancer (OC) causes significant morbidity and mortality as neither detection nor screening of OC is currently feasible at an early stage. Difficulty to promptly diagnose OC in its early stage remains challenging due to non-specific symptoms in the early-stage of the disease, their presentation at an advanced stage and poor survival. Therefore, improved detection methods are urgently needed. In this article, we summarize the potential clinical utility of epigenetic signatures like DNA methylation, histone modifications, and microRNA dysregulation, which play important role in ovarian carcinogenesis and discuss its application in development of diagnostic, prognostic, and predictive biomarkers. Molecular characterization of epigenetic modification (methylation) in circulating cell free tumor DNA in body fluids offers novel, non-invasive approach for identification of potential promising cancer biomarkers, which can be performed at multiple time points and probably better reflects the prevailing molecular profile of cancer. Current status of epigenetic research in diagnosis of early OC and its management are discussed here with main focus on potential diagnostic biomarkers in tissue and body fluids. Rapid and point of care diagnostic applications of DNA methylation in liquid biopsy has been precluded as a result of cumbersome sample preparation with complicated conventional methods of isolation. New technologies which allow rapid identification of methylation signatures directly from blood will facilitate sample-to answer solutions thereby enabling next-generation point of care molecular diagnostics. To date, not a single epigenetic biomarker which could accurately detect ovarian cancer at an early stage in either tissue or body fluid has been reported. Taken together, the methodological drawbacks, heterogeneity associated with ovarian cancer and non-validation of the clinical utility of reported potential biomarkers in larger ovarian cancer populations has impeded the transition of epigenetic biomarkers from lab to clinical settings. Until addressed, clinical implementation as a diagnostic measure is a far way to go.

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C/EBPβ enhances platinum resistance of ovarian cancer cells by reprogramming H3K79 methylation

Cited by 95 publications

References 70 publications

PGC1α/CEBPB/CPT1A axis promotes radiation resistance of nasopharyngeal carcinoma through activating fatty acid oxidation

PGC1α/CEBPB/CPT1A axis promotes radiation resistance of nasopharyngeal carcinoma through activating fatty acid oxidation

Truncated Bid Regulates Cisplatin Response via Activation of Mitochondrial Apoptosis Pathway in Ovarian Cancer

Epigenetic Biomarkers in the Management of Ovarian Cancer: Current Prospectives

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