دورية أكاديمية
RNA binding protein RALY facilitates colorectal cancer metastasis via enhancing exosome biogenesis in m6A dependent manner.
| العنوان: | RNA binding protein RALY facilitates colorectal cancer metastasis via enhancing exosome biogenesis in m6A dependent manner. |
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| المؤلفون: | Zhou J; Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315000, China; Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China., Li L; Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China., Han Y; Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China., Ge G; Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: geguangbo@shutcm.edu.cn., Ji Q; Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: ttt99118@hotmail.com., Li H; Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315000, China. Electronic address: lihongshan_1982@126.com. |
| المصدر: | International journal of biological macromolecules [Int J Biol Macromol] 2024 Jul; Vol. 273 (Pt 2), pp. 133112. Date of Electronic Publication: 2024 Jun 14. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7909578 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0003 (Electronic) Linking ISSN: 01418130 NLM ISO Abbreviation: Int J Biol Macromol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Original Publication: Guildford, Eng., IPC Science and Technology Press. |
| مواضيع طبية MeSH: | Colorectal Neoplasms*/pathology , Colorectal Neoplasms*/metabolism , Colorectal Neoplasms*/genetics , Exosomes*/metabolism , Neoplasm Metastasis* , RNA-Binding Proteins*/metabolism , RNA-Binding Proteins*/genetics, Animals ; Humans ; Mice ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Multivesicular Bodies/metabolism ; Phospholipase D/metabolism ; Phospholipase D/genetics |
| مستخلص: | Tumor metastasis is the leading cause of cancer-related death in patients with colorectal cancer (CRC). Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA-binding proteins, involved in the tumorigenesis and metastasis of various cancers. However, the molecular mechanisms of hnRNPs in CRC metastasis remain unclear. This study aims to uncover the pivotal roles and molecular mechanisms of hnRNPs in CRC metastasis. Clinical database analysis suggested that the expression of hnRNP-Associated with Lethal Yellow (RALY, an important member of hnRNPs) was strongly correlated with the aggressiveness and survival of CRC patients. Gain- and loss-of-function studies demonstrated that RALY promotes the production of exosomes by increasing the formation of multivesicular bodies (MVBs) and enhancing the fusion of MVBs with the plasma membrane. Notably, RALY directly interacts with phospholipase D2 (PLD2) to enable exosome biogenesis, and cooperates with RBM15b to control PLD2 mRNA stability in an m6A-dependent manner. RALY-mediated exosome secretion activates pro-tumor macrophages and further facilitates CRC metastasis, while rescue experiments in vivo further confirmed that RALY-mediated exosome biogenesis facilitates CRC metastasis. Collectively, our findings demonstrate that RALY promotes exosome biogenesis and facilitates colorectal cancer metastasis by upregulating PLD2 and enhancing exosome production in an m6A-dependent manner, suggesting potential therapeutic strategies for combating CRC metastasis. Competing Interests: Declaration of competing interest The authors declare that they have no competing interests. (Copyright © 2024. Published by Elsevier B.V.) |
| فهرسة مساهمة: | Keywords: Colorectal cancer metastasis; Exosome; RALY |
| المشرفين على المادة: | EC 3.1.4.4 (Phospholipase D) 0 (RNA-Binding Proteins) 0 (RALY protein, human) |
| تواريخ الأحداث: | Date Created: 20240616 Date Completed: 20240706 Latest Revision: 20240731 |
| رمز التحديث: | 20240731 |
| DOI: | 10.1016/j.ijbiomac.2024.133112 |
| PMID: | 38880454 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-0003 |
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| DOI: | 10.1016/j.ijbiomac.2024.133112 |