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T-Box Transcription Factor 2 Enhances Chemoresistance of Endometrial Cancer by Mediating NRF2 Expression
Ning Ding1, Ting Zhang1, Xiaohui Yu1
1Department of Gynaecology, Zibo Central Hospital, No. 54 Gongqingtuan Road, Zhangdian District, Zibo 255036, Shandong, China.
Background:
The roles of T-Box transcription factor (TBX2) in endometrial cancer are still not clear. This study was designed to explore the roles of TBX2 in endometrial cancer and the underlying mechanisms.
Methods:
The knockdown and overexpression of TBX2 in endometrial cancer cell lines were constructed by using lentivirus transduction. The xenograft animal model was established by using stable endometrial cancer cell lines. Cell viability was determined by the CCK-8 assay. The mRNA and protein levels of target genes were determined by using qPCR and Western blotting, respectively. ChIP assay was used to determine the interactions between TBX2 and nuclear factor erythroid 2-related factor 2 (NRF2).
Results:
The upregulation of TBX2 was observed in endometrial cancer tissues from patients with Cisplatin- resistance and Cisplatin-resistant cells. Interestingly, TBX2 regulated cell viability and Cisplatin resistance of endometrial cancer cells. In addition, the regulatory effects of TBX2 on chemo-resistance of endometrial cancer cells were associated with the NRF2 signaling pathways. Consistently, the endometrial cancer xenograft animal model revealed that TBX2 regulated tumor growth and Cisplatin resistance, and its regulatory effects were in part by the regulation of NRF2 signaling pathways.
Conclusion:
TBX 2 enhanced Cisplatin resistance of endometrial cancer by regulating the NRF2 signaling pathways.
Insights
T-Box transcription factor 2 (TBX2) enhances cisplatin resistance in endometrial cancer. This occurs by regulating the nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway, impacting cell viability and tumor growth.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The role of T-Box transcription factor 2 (TBX2) in endometrial cancer remains unclear.
- Investigating TBX2's function and mechanisms in endometrial cancer is crucial for understanding treatment resistance.
Purpose of the Study:
- To explore the role of TBX2 in endometrial cancer.
- To elucidate the underlying mechanisms by which TBX2 influences endometrial cancer progression and chemoresistance.
Main Methods:
- TBX2 expression was manipulated (knockdown/overexpression) in endometrial cancer cell lines using lentivirus transduction.
- Cell viability was assessed via CCK-8 assay; gene and protein levels were analyzed by qPCR and Western blotting.
- Interactions between TBX2 and nuclear factor erythroid 2-related factor 2 (NRF2) were investigated using ChIP assays and xenograft models.
Main Results:
- TBX2 was found to be upregulated in cisplatin-resistant endometrial cancer tissues and cells.
- TBX2 significantly regulated cell viability and cisplatin resistance in endometrial cancer.
- TBX2's effects on chemoresistance were linked to the NRF2 signaling pathway, confirmed in both cell lines and a xenograft model.
Conclusions:
- TBX2 plays a key role in enhancing cisplatin resistance in endometrial cancer.
- The mechanism involves the regulation of the NRF2 signaling pathway by TBX2.
- Targeting TBX2 or the NRF2 pathway may offer therapeutic strategies for overcoming chemoresistance in endometrial cancer.
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