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Transducin β-like 1 X-linked receptor 1 suppresses cisplatin sensitivity in nasopharyngeal carcinoma via activation
Shu-Peng Chen, Qi Yang, Chan-Juan Wang
1Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in South China Guangzhou, Guangdong 510060, People's Republic of China. guoxiang@sysucc.org.cn.
Background:
Transducin β-like 1 X-linked receptor 1 (TBL1XR1) is an important transcriptional cofactor involved in the regulation of many signaling pathways, and is associated with carcinogenesis and tumor progression. However, the precise role of TBL1XR1 in these processes is not well understood.
Methods:
We detected the expression of TBL1XR1 protein and mRNA in nasopharyngeal carcinoma (NPC) cell lines and biopsies by western blotting, real-time PCR and immunohistochemical staining (IHC). Overexpression of TBL1XR1 in NPC enhanced chemoresistance to cisplatin using two NPC cell lines in vitro and in vivo.
Results:
TBL1XR1 was upregulated in NPC cell lines and clinical samples. The expression of TBL1XR1 was correlated with several clinicopathological factors including clinical stage, T classification, N classification and patient survival. Univariate and multivariate analysis revealed that TBL1XR1 was an independent prognostic factor for patient survival. In vitro and in vivo studies demonstrated that TBL1XR1 high expression induced resistance to cisplatin-induced apoptosis in NPC cells. Furthermore, we found that TBL1XR1 activated the NF-κB pathway and promoted transcription of genes downstream of NF-κB, especially anti-apoptotic genes.
Conclusions:
Upregulation of TBL1XR1 induces NPC cells resistance to cisplatin by activating the NF-κB pathway, and correlates with poor overall survival of NPC patients. TBL1XR1 has a pivotal role in NPC and could be a valuable prognostic factor as well as a novel biomarker for tailoring appropriate therapeutic regimes.
Insights
Transducin β-like 1 X-linked receptor 1 (TBL1XR1) upregulation in nasopharyngeal carcinoma (NPC) promotes cisplatin resistance by activating the NF-κB pathway. This finding suggests TBL1XR1 is a prognostic factor and potential therapeutic target for NPC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Transducin β-like 1 X-linked receptor 1 (TBL1XR1) is a transcriptional cofactor implicated in various signaling pathways and cancer.
- Its specific role in carcinogenesis and tumor progression, particularly in nasopharyngeal carcinoma (NPC), remains unclear.
Purpose of the Study:
- To investigate the role of TBL1XR1 in nasopharyngeal carcinoma (NPC).
- To determine the association between TBL1XR1 expression and chemoresistance to cisplatin.
- To explore TBL1XR1 as a prognostic marker in NPC.
Main Methods:
- TBL1XR1 protein and mRNA expression were analyzed in NPC cell lines and patient biopsies using western blotting, real-time PCR, and immunohistochemistry.
- Chemoresistance to cisplatin was assessed in NPC cell lines in vitro and in vivo following TBL1XR1 overexpression.
- The NF-κB signaling pathway activation was investigated in relation to TBL1XR1 expression.
Main Results:
- TBL1XR1 was found to be upregulated in NPC cell lines and clinical samples.
- High TBL1XR1 expression correlated with advanced clinical stage, T classification, N classification, and poorer patient survival.
- Overexpression of TBL1XR1 conferred resistance to cisplatin-induced apoptosis in NPC cells, mediated by activation of the NF-κB pathway and increased transcription of anti-apoptotic genes.
Conclusions:
- Upregulated TBL1XR1 contributes to cisplatin resistance in NPC by activating the NF-κB pathway.
- TBL1XR1 expression is a significant independent prognostic factor for overall survival in NPC patients.
- TBL1XR1 represents a potential therapeutic target and biomarker for personalized treatment strategies in NPC.
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