FBP1 knockdown decreases ovarian cancer formation and cisplatin resistance through EZH2-mediated H3K27me3
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Xifeng Xiong1, Xudong Lai2, Jinli Zhang1
1Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou 510220, China.
Abstract:
Worldwide, ovarian cancer (OC) is the seventh common cancer and the second most common cause of cancer death in women. Due to high rates of relapse, there is an urgent need for the identification of new targets for OC treatment. The far-upstream element binding protein 1 (FBP1) and enhancer of zeste homolog 2 (EZH2) are emerging proto-oncogenes that regulate cell proliferation and metastasis. In the present study, Oncomine data analysis demonstrated that FBP1 was closely associated with the development of OC, and The Cancer Genome Atlas (TCGA) data analysis indicated that there was a positive correlation between FBP1 and EZH2 in ovarian tissues. Moreover, we found that FBP1 knockdown suppressed tumor formation in nude mice and cisplatin resistance of OC cells, but the role of FBP1 in the cisplatin resistance of OC cells remained unclear. In addition, we verified physical binding between FBP1 and EZH2 in OC cells, and we demonstrated that FBP1 knockdown enhanced cisplatin cytotoxicity in OC cells and down-regulated EZH2 expression and trimethylation of H3K27. These results suggested that FBP1 increases cisplatin resistance of OC cells by up-regulating EZH2/H3K27me3. Thus, FBP1 is a prospective novel target for the development of OC treatment.
Insights
Far-upstream element binding protein 1 (FBP1) drives ovarian cancer (OC) cisplatin resistance by increasing enhancer of zeste homolog 2 (EZH2) expression. Targeting FBP1 may offer a new therapeutic strategy for ovarian cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Ovarian cancer (OC) is a leading cause of cancer death in women, with high relapse rates necessitating novel therapeutic targets.
- Far-upstream element binding protein 1 (FBP1) and enhancer of zeste homolog 2 (EZH2) are proto-oncogenes implicated in cancer progression.
Purpose of the Study:
- To investigate the role of FBP1 in ovarian cancer development and cisplatin resistance.
- To elucidate the relationship between FBP1 and EZH2 in ovarian cancer.
Main Methods:
- Oncomine and The Cancer Genome Atlas (TCGA) data analysis to assess FBP1 and EZH2 correlation in ovarian tissues.
- In vivo tumor formation studies in nude mice.
- In vitro experiments involving FBP1 knockdown in OC cells to evaluate cisplatin resistance and EZH2/H3K27me3 expression.
Main Results:
- FBP1 expression is associated with OC development and positively correlates with EZH2 in ovarian tissues.
- FBP1 knockdown suppressed tumor formation and reduced cisplatin resistance in OC cells.
- FBP1 physically interacts with EZH2, and FBP1 knockdown down-regulates EZH2 expression and H3K27 trimethylation, enhancing cisplatin cytotoxicity.
Conclusions:
- FBP1 promotes cisplatin resistance in ovarian cancer by up-regulating the EZH2/H3K27me3 pathway.
- FBP1 represents a potential therapeutic target for overcoming cisplatin resistance in ovarian cancer treatment.
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