LncRNA PVT1 promotes exosome secretion through YKT6, RAB7, and VAMP3 in pancreatic cancer

• DOI: 10.18632/aging.103268
• Publication Date: 2020-06-05T01:40:11Z
• Authors: Chengming Sun; Peng Wang; Wei Dong; Haishi Liu; Jianmin Sun; Liang Zhao
• Keywords: 0303 health sciences; Vesicle-Associated Membrane Protein 3; Lipoylation; Cell Membrane; Multivesicular Bodies; rab7 GTP-Binding Proteins; Exosomes; Up-Regulation; 3. Good health; Gene Expression Regulation, Neoplastic; Pancreatic Neoplasms; R-SNARE Proteins; 03 medical and health sciences; Microscopy, Electron, Transmission; rab GTP-Binding Proteins; Cell Line, Tumor; Tumor Microenvironment; Humans; RNA, Long Noncoding; Research Paper

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.