Abstract
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.
Highlights
Pancreatic cancer (PC) is one of the most devastating and fatal malignancies with poor prognosis and high mortality worldwide, manifesting the close parallel correlation between incidence and mortality [1]
The results obtained from qRT-Real-time PCR (PCR) revealed that plasmacytoma variant translocation 1 (PVT1) was increased in all four tested PC cell lines (Figure 1A), which was consistent with previous findings [14, 16, 29]
The results showed that the expressions of YKT6, RAB7, and vesicle-associated membrane protein 3 (VAMP3) were upregulated in PC cells (Figure 1B–1D)
Summary
Pancreatic cancer (PC) is one of the most devastating and fatal malignancies with poor prognosis and high mortality worldwide, manifesting the close parallel correlation between incidence and mortality [1]. Less than 10% of patients with PC are diagnosed at an early phase. Most of the patients lack the opportunity to receive surgical treatment due to being diagnosed at a later phase [2]. The high mortality is primarily attributed to several factors, for example, family history, genetics, cigarette consumption, and chronic pancreatitis [1]. The key reason for high mortality is the advanced stage at which most patients are diagnosed [3]. Another challenge for PC treatment is that patients with PC respond poorly to either radiotherapy or chemotherapy [4]. The exploration of the mechanism underlying the pathology and progression of PC is urgently needed
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