Exosomal lncRNA XIST promotes perineural invasion of pancreatic cancer cells via miR-211-5p/GDNF.

Autor: Cheng K; The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116044, China., Pan J; The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116044, China., Liu Q; The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116044, China., Ji Y; The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116044, China., Liu L; The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116044, China., Guo X; Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Software, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, 47500, China., Wang Q; Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Software, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, 47500, China., Li S; College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China., Sun J; The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116044, China., Gong M; The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116044, China. gongmiaomiao1029@163.com., Zhang Y; Sixth Department of liver disease, Dalian Public Health Clinical Center, Dalian, 116044, China. zy730302@aliyun.com., Yuan Y; The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116044, China. yuhuiyuan@hotmail.com.
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2024 May; Vol. 43 (18), pp. 1341-1352. Date of Electronic Publication: 2024 Mar 07.
DOI: 10.1038/s41388-024-02994-6
Abstrakt: Perineural invasion (PNI) is an essential form of tumor metastasis in multiple malignant cancers, such as pancreatic cancer, prostate cancer, and head and neck cancer. Growing evidence has revealed that pancreatic cancer recurrence and neuropathic pain positively correlate with PNI. Therefore, targeting PNI is a proper strategy for pancreatic cancer treatment. Exosomal lncRNA derived from pancreatic cancer cells is an essential component of the tumor microenvironment. However, whether exosomal lncXIST derived from pancreatic cancer cells can promote PNI and its exact mechanism remains to be elucidated. We show that lncXIST mediates nerve-tumor crosstalk via exosomal delivery. Our data reveal that exosomal lncXIST derived from pancreatic cancer cells is delivered to neural cells and promotes their release of glial-cell-line-derived neurotrophic factor (GDNF), essential in facilitating the PNI of pancreatic cancer. Mechanistically, microRNA-211-5p negatively regulates GDNF, and lncXIST serves as a miR-211-5p sponge. The function of exosomes in the dynamic interplay between nerves and cancer is confirmed in both in vivo and in vitro PNI models. Therefore, targeting pancreatic cancer cell-derived exosomal lncXIST may provide clues for a promising approach for developing a new strategy to combat PNI of pancreatic cancer.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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