# LncRNA PVT1 promotes exosome secretion through YKT6, RAB7, and VAMP3 in pancreatic cancer **Authors:** Chengming Sun, Peng Wang, Wei Dong, Haishi Liu, Jianmin Sun, Liang Zhao PMC · DOI: 10.18632/aging.103268 · Aging (Albany NY) · 2020-06-04 ## TL;DR The lncRNA PVT1 increases exosome production in pancreatic cancer by regulating proteins like YKT6, RAB7, and VAMP3, which may help cancer spread. ## Contribution This study reveals a novel role of PVT1 in promoting exosome secretion in pancreatic cancer through specific molecular mechanisms involving YKT6, RAB7, and VAMP3. ## Key findings - PVT1 is upregulated in pancreatic cancer cells and increases exosome secretion. - PVT1 promotes multivesicular body transport and fusion with the plasma membrane via YKT6, RAB7, and VAMP3. - PVT1 alters RAB7 localization and YKT6 palmitoylation to enhance exosome release. ## 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. ## Linked entities - **Genes:** PVT1 (Pvt1 oncogene) [NCBI Gene 5820], YKT6 (YKT6 vesicular SNARE protein) [NCBI Gene 10652], RAB7A (RAB7A, member RAS oncogene family) [NCBI Gene 7879], VAMP3 (vesicle associated membrane protein 3) [NCBI Gene 9341] - **Diseases:** pancreatic cancer (MONDO:0005192) ## Full-text entities - **Genes:** RAB7B (RAB7B, member RAS oncogene family) [NCBI Gene 338382] {aka RAB7}, SERPINE1 (serpin family E member 1) [NCBI Gene 5054] {aka PAI, PAI-1, PAI1, PLANH1}, YKT6 (YKT6 vesicular SNARE protein) [NCBI Gene 10652], RAB27B (RAB27B, member RAS oncogene family) [NCBI Gene 5874] {aka C25KG}, RAB35 (RAB35, member RAS oncogene family) [NCBI Gene 11021] {aka H-ray, RAB1C, RAY}, RAB9A (RAB9A, member RAS oncogene family) [NCBI Gene 9367] {aka RAB9}, RAB11A (RAB11A, member RAS oncogene family) [NCBI Gene 8766] {aka YL8}, PVT1 (Pvt1 oncogene) [NCBI Gene 5820] {aka LINC00079, MIR1204HG, NCRNA00079, TP53LC09, onco-lncRNA-100}, TSG101 (tumor susceptibility 101) [NCBI Gene 7251] {aka TSG10, VPS23}, POTEF (POTE ankyrin domain family member F) [NCBI Gene 728378] {aka A26C1B, POTE2alpha, POTEACTIN}, SNAR-E (small NF90 (ILF3) associated RNA E) [NCBI Gene 100170220], VTI1B (vesicle transport through interaction with t-SNAREs 1B) [NCBI Gene 10490] {aka VTI1, VTI1-LIKE, VTI1L, VTI2, v-SNARE, vti1-rp1}, PDCD6IP (programmed cell death 6 interacting protein) [NCBI Gene 10015] {aka AIP1, ALIX, DRIP4, HP95, MCPH29}, CD63 (CD63 molecule) [NCBI Gene 967] {aka AD1, HOP-26, ME491, MLA1, OMA81H, Pltgp40}, MIR448 (microRNA 448) [NCBI Gene 554212] {aka MIRN448, hsa-mir-448, miRNA448}, RAB5A (RAB5A, member RAS oncogene family) [NCBI Gene 5868] {aka RAB5}, VAMP7 (vesicle associated membrane protein 7) [NCBI Gene 6845] {aka SYBL1, TI-VAMP, TIVAMP, VAMP-7}, SNAP23 (synaptosome associated protein 23) [NCBI Gene 8773] {aka HsT17016, SNAP-23, SNAP23A, SNAP23B}, AGFG1 (ArfGAP with FG repeats 1) [NCBI Gene 3267] {aka HRB, RAB, RIP}, WNT3A (Wnt family member 3A) [NCBI Gene 89780], RAB6A (RAB6A, member RAS oncogene family) [NCBI Gene 5870] {aka RAB6}, RAB27A (RAB27A, member RAS oncogene family) [NCBI Gene 5873] {aka GS2, HsT18676, RAB27, RAM}, VAMP3 (vesicle associated membrane protein 3) [NCBI Gene 9341] {aka CEB}, SDCBP (syndecan binding protein) [NCBI Gene 6386] {aka MDA-9, MDA9, SDCBP1, ST1, SYCL, TACIP18}, RAB2B (RAB2B, member RAS oncogene family) [NCBI Gene 84932] - **Diseases:** tumorigenesis (MESH:D063646), PC (MESH:D010190), metastasis (MESH:D009362), chronic pancreatitis (MESH:D050500), death (MESH:D003643), breast cancer (MESH:D001943), lung cancer (MESH:D008175), Cancer (MESH:D009369) - **Chemicals:** carbon (MESH:D002244), DAPI (MESH:C007293), SYBR Green (MESH:C098022), CO2 (MESH:D002245), Biotin (MESH:D001710), Gemcitabine (MESH:D000093542), SDS (MESH:D012967), Triton X-100 (MESH:D017830), Coomassie Brilliant Blue G-250 (MESH:C004692), paraformaldehyde (MESH:C003043), PBS (MESH:D007854), uranyl acetate (MESH:C005460), water (MESH:D014867), TRIzol (MESH:C411644), DMEM (-) - **Species:** Mus musculus (house mouse, species) [taxon 10090], Mycoplasma (genus) [taxon 2093], Homo sapiens (human, species) [taxon 9606] - **Cell lines:** H6C7 — Homo sapiens (Human), Transformed cell line (CVCL_0P38), PANC-1 — Homo sapiens (Human), Pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_0480), HEK293 — Homo sapiens (Human), Transformed cell line (CVCL_0045), HS766T — Homo sapiens (Human), Pancreatic adenocarcinoma, Cancer cell line (CVCL_0334), ASPC-1 — Homo sapiens (Human), Pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_0152), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031), MIA PaCa-2 — Homo sapiens (Human), Pancreatic undifferentiated carcinoma, Cancer cell line (CVCL_0428), BxPC3 — Homo sapiens (Human), Pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_0186) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC7346024/full.md ## Figures 6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC7346024/full.md ## References 62 references — full list in the complete paper: https://tomesphere.com/paper/PMC7346024/full.md --- Source: https://tomesphere.com/paper/PMC7346024