Modulation of the PGRMC1/NLRP7/HLA-C axis by autophagy is linked to both spontaneous preterm birth and gestational choriocarcinoma
Abstract
Spontaneous preterm birth (SPTB) and gestational choriocarcinoma are both associated with complex physiological processes that significantly impact maternal health. While the molecular mechanisms underlying SPTB and gestational choriocarcinoma remain poorly understood, emerging evidence suggests that immune regulation plays a crucial role in both conditions. In this study, we revealed that progesterone regulates autophagy via the noncanonical progesterone receptor membrane component 1 (PGRMC1), which then modulates NLRP7 levels, thereby impacting HLA-C expression in the JEG3 cell line, an extravillous trophoblast (EVT) model. Furthermore, a significant positive correlation between NLRP7 and HLA-C expression was observed in EVTs from placental tissues and choriocarcinoma samples. In cases of SPTB, we found both reduced expression of NLRP7 and HLA-C in EVTs. Similarly, in gestational choriocarcinoma samples, we observed significantly lower expression levels of NLRP7 and HLA-C, further suggesting a shared immune evasion mechanism. These findings not only provide insights into the molecular mechanisms underlying both SPTB and choriocarcinoma but also identify the progesterone-driven NLRP7/HLA-C axis as a promising target for therapeutic intervention, offering strategies for improving outcomes in both conditions.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (13)
Qin Li
Huaxiao Yu
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
Dongyi Ling
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center
Jie Zhou
Shanshan Zhen
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center
Yangyang Li
Hefei National Laboratory for Physical Sciences at the Microscale, Key Laboratory of Surface and Interface Chemistry and Energy Catalysis of Anhui Higher Education Institutes, School of Chemistry and Materials Science
Lijuan Wang
Zetong Zheng
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
Wenjian Cen
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center
Hongyi Gao
Department of Pathology, Guangdong Women and Children Hospital
Hui Chen
Jack L. Strominger
Department of Stem Cell and Regenerative Biology, Harvard University
Ziming Du
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center