Research Paper Volume 12, Issue 11 pp 10427—10440
LncRNA PVT1 promotes exosome secretion through YKT6, RAB7, and VAMP3 in pancreatic cancer
- 1 Department of Hepatopancreatobiliary Surgery, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang, China
Received: February 13, 2020 Accepted: April 20, 2020 Published: June 4, 2020https://doi.org/10.18632/aging.103268
How to Cite
Copyright © 2020 Sun et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
PC: Pancreatic cancer; lncrnas: Long non-coding rnas; PVT1: Plasmacytoma variant translocation 1; RAB7: Ras-related protein Rab-7; VAMP3: Vesicle-associated membrane protein 3; mvbs: Multivesicular bodies; H6C7: Human Pancreatic Duct Epithelial Cell Line; ATCC: American Type Culture Collection; DMEM: Dulbecco’s Modified Eagle Medium; sirab7: Small interfering rnas for RAB7; TEM: Transmission electron microscopy; qrt- PCR: Real-time PCR; SD: Standard deviation; Snares: Soluble N-ethylmaleimide-sensitive factor attachment protein receptors.