J Pathol Transl Med.
2025 Jan;59(1):68-83. 10.4132/jptm.2024.11.27.
PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in nasopharyngeal carcinoma
- Feng R
1,2 - Guo Y1,3
- Chen M4
- Tian Z1,5
- Liu Y1,5
- Jiang S1,5
- Zhou J1,5
- Liu Q1,5
- Li X6
- Xiong W7,8
- Shi L9
- Fan S9
- Li G7,8
- Zhang W1,5
- Affiliations
-
- 1Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, China
- 2Department of Laboratory Medicine, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China
- 3Department of Blood Transfusion, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China
- 4The First Affiliated Hospital of Sun Yatsen University, Guangzhou, China
- 5Department of Medical Laboratory Science , Xiangya School of Medicine, Central South University, Changsha, China
- 6Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, China
- 7NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- 8The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medicine Sciences, Central South University, Changsha, China
- 9Department of Pathology, Second Xiangya Hospital, Central South University, Changsha, China
- KMID: 2563886
- DOI: http://doi.org/10.4132/jptm.2024.11.27
Abstract
- Background
Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear.
Methods
We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP).
Results
We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin.
Conclusions
PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.
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