LncRNA PVT1 promotes exosome secretion through YKT6, RAB7, and VAMP3 in pancreatic cancer
| Autor: | Peng Wang, Wei Dong, Liang Zhao, Chengming Sun, Haishi Liu, Jianmin Sun |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
exosome secretion
Aging Vesicle-Associated Membrane Protein 3 Lipoylation pancreatic cancer YKT6 medicine.disease_cause Exosomes Exosome R-SNARE Proteins Palmitoylation Microscopy Electron Transmission RAB7 Cell Line Tumor medicine Tumor Microenvironment Humans Secretion PVT1 VAMP3 Chemistry Cell Membrane Multivesicular Bodies rab7 GTP-Binding Proteins Cell Biology Microvesicles Cell biology Up-Regulation Gene Expression Regulation Neoplastic Pancreatic Neoplasms Membrane protein rab GTP-Binding Proteins Cancer cell RNA Long Noncoding Carcinogenesis Research Paper |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | Pancreatic cancer (PC) is one of the deadliest cancers worldwide. Cancer cells secrete excessive numbers of exosomes that play essential roles in tumorigenesis. Long non-coding RNAs (lncRNAs) are essential non-coding RNAs for cancer progression. However, the role of lncRNA plasmacytoma variant translocation 1 (PVT1) in exosome secretion of PC remains to be comprehensively investigated. Thus, nanoparticle tracking analysis and transmission electron microscopy were performed to determine exosome secretion. Confocal microscopy, western blots, real-time PCR, immunofluorescence, pull-down and RNA immunoprecipitation assays, and rescue experiments were applied to investigate the mechanism underlying the role of PVT1 in exosome secretion. The results showed that PVT1 was upregulated in PC cells, along with increased levels of YKT6 v-SNARE homolog (YKT6), ras-related protein Rab-7 (RAB7), and vesicle-associated membrane protein 3 (VAMP3). Also, PVT1 promoted the transportation of multivesicular bodies (MVBs) towards the plasma membrane. In addition, PVT1 promoted the docking of MVBs by altering RAB7 expression and localization. Moreover, PVT1 promoted the fusion of MVBs with the plasma membrane through regulating YKT6 and VAMP3 colocalization and the palmitoylation of YKT6. Taken together, the results suggest that PVT1 promoted exosome secretion of PC cells and thus, can expand the understanding of PVT1 in tumor biology. |
| Databáze: | OpenAIRE |
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