Extracellular Vesicle-Loaded Oncogenic lncRNA NEAT1 from Adipose-Derived Mesenchymal Stem Cells Confers Gemcitabine Resistance in Pancreatic Cancer via miR-491-5p/Snail/SOCS3 Axis
It is becoming increasingly evident that key mechanisms of mesenchymal stem cell (MSC) efficacy appear to associate with paracrine activities, and the delivery of cargos through extracellular vesicles (EVs) controls the mechanistic actions of MSCs. Thus, this study clarified a possible mechanism by...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-01-01
|
| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2023/6510571 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832551195752792064 |
|---|---|
| author | Rongxiang Wu Zhan Su Le Zhao Ruifeng Pei Yiren Ding Deqiang Li Shuo Zhu Lu Xu Wei Zhao Wuyuan Zhou |
| author_facet | Rongxiang Wu Zhan Su Le Zhao Ruifeng Pei Yiren Ding Deqiang Li Shuo Zhu Lu Xu Wei Zhao Wuyuan Zhou |
| author_sort | Rongxiang Wu |
| collection | DOAJ |
| description | It is becoming increasingly evident that key mechanisms of mesenchymal stem cell (MSC) efficacy appear to associate with paracrine activities, and the delivery of cargos through extracellular vesicles (EVs) controls the mechanistic actions of MSCs. Thus, this study clarified a possible mechanism by which EV-encapsulated NEAT1 from adipose-derived mesenchymal stem cells (ADSCs) might mediate gemcitabine resistance in pancreatic cancer (PCa). Microarray profile suggested a differentially expressed lncRNA NEAT1 in PCa, and we determined its expression in PCa cells. NEAT1 was found to be upregulated in PCa. The binding affinity among NEAT1, miR-491-5p, and Snail was identified through bioinformatic analysis and experimental validation. NEAT1 competitively bound to miR-491-5p to elevate Snail expression and diminish SOCS3 expression. PCa cells were cocultured with EVs extracted from ADSCs, followed by assessment of malignant phenotypes, tumorigenesis, and gemcitabine resistance of PCa cells using gain- or loss-of-function experiments. ADSC-derived EVs carrying NEAT1 promoted PCa cell proliferation, migration, and gemcitabine resistance in vitro and enhanced tumorigenicity in vivo by inhibiting miR-491-5p and SOCS3 and upregulating Snail. Collectively, the findings from our study found a new potential strategy for gemcitabine resistance in PCa by illustrating the mechanistic insights of oncogenic ADSC-derived EVs-loaded NEAT1 via regulating the miR-491-5p/Snail/SOCS3 axis. |
| format | Article |
| id | doaj-art-7dbf331ea2614807bde7685cc4a7a20f |
| institution | Kabale University |
| issn | 1687-9678 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-7dbf331ea2614807bde7685cc4a7a20f2025-02-03T06:04:46ZengWileyStem Cells International1687-96782023-01-01202310.1155/2023/6510571Extracellular Vesicle-Loaded Oncogenic lncRNA NEAT1 from Adipose-Derived Mesenchymal Stem Cells Confers Gemcitabine Resistance in Pancreatic Cancer via miR-491-5p/Snail/SOCS3 AxisRongxiang Wu0Zhan Su1Le Zhao2Ruifeng Pei3Yiren Ding4Deqiang Li5Shuo Zhu6Lu Xu7Wei Zhao8Wuyuan Zhou9Jiangsu UniversityDepartment of Hepatopancreatobiliary SurgeryDepartment of Hepatopancreatobiliary SurgeryDepartment of Hepatopancreatobiliary SurgeryDepartment of Hepatopancreatobiliary SurgeryDepartment of Hepatopancreatobiliary SurgeryDepartment of Hepatopancreatobiliary SurgeryDepartment of Hepatopancreatobiliary SurgeryDepartment of Hepatopancreatobiliary SurgeryDepartment of Hepatopancreatobiliary SurgeryIt is becoming increasingly evident that key mechanisms of mesenchymal stem cell (MSC) efficacy appear to associate with paracrine activities, and the delivery of cargos through extracellular vesicles (EVs) controls the mechanistic actions of MSCs. Thus, this study clarified a possible mechanism by which EV-encapsulated NEAT1 from adipose-derived mesenchymal stem cells (ADSCs) might mediate gemcitabine resistance in pancreatic cancer (PCa). Microarray profile suggested a differentially expressed lncRNA NEAT1 in PCa, and we determined its expression in PCa cells. NEAT1 was found to be upregulated in PCa. The binding affinity among NEAT1, miR-491-5p, and Snail was identified through bioinformatic analysis and experimental validation. NEAT1 competitively bound to miR-491-5p to elevate Snail expression and diminish SOCS3 expression. PCa cells were cocultured with EVs extracted from ADSCs, followed by assessment of malignant phenotypes, tumorigenesis, and gemcitabine resistance of PCa cells using gain- or loss-of-function experiments. ADSC-derived EVs carrying NEAT1 promoted PCa cell proliferation, migration, and gemcitabine resistance in vitro and enhanced tumorigenicity in vivo by inhibiting miR-491-5p and SOCS3 and upregulating Snail. Collectively, the findings from our study found a new potential strategy for gemcitabine resistance in PCa by illustrating the mechanistic insights of oncogenic ADSC-derived EVs-loaded NEAT1 via regulating the miR-491-5p/Snail/SOCS3 axis.http://dx.doi.org/10.1155/2023/6510571 |
| spellingShingle | Rongxiang Wu Zhan Su Le Zhao Ruifeng Pei Yiren Ding Deqiang Li Shuo Zhu Lu Xu Wei Zhao Wuyuan Zhou Extracellular Vesicle-Loaded Oncogenic lncRNA NEAT1 from Adipose-Derived Mesenchymal Stem Cells Confers Gemcitabine Resistance in Pancreatic Cancer via miR-491-5p/Snail/SOCS3 Axis Stem Cells International |
| title | Extracellular Vesicle-Loaded Oncogenic lncRNA NEAT1 from Adipose-Derived Mesenchymal Stem Cells Confers Gemcitabine Resistance in Pancreatic Cancer via miR-491-5p/Snail/SOCS3 Axis |
| title_full | Extracellular Vesicle-Loaded Oncogenic lncRNA NEAT1 from Adipose-Derived Mesenchymal Stem Cells Confers Gemcitabine Resistance in Pancreatic Cancer via miR-491-5p/Snail/SOCS3 Axis |
| title_fullStr | Extracellular Vesicle-Loaded Oncogenic lncRNA NEAT1 from Adipose-Derived Mesenchymal Stem Cells Confers Gemcitabine Resistance in Pancreatic Cancer via miR-491-5p/Snail/SOCS3 Axis |
| title_full_unstemmed | Extracellular Vesicle-Loaded Oncogenic lncRNA NEAT1 from Adipose-Derived Mesenchymal Stem Cells Confers Gemcitabine Resistance in Pancreatic Cancer via miR-491-5p/Snail/SOCS3 Axis |
| title_short | Extracellular Vesicle-Loaded Oncogenic lncRNA NEAT1 from Adipose-Derived Mesenchymal Stem Cells Confers Gemcitabine Resistance in Pancreatic Cancer via miR-491-5p/Snail/SOCS3 Axis |
| title_sort | extracellular vesicle loaded oncogenic lncrna neat1 from adipose derived mesenchymal stem cells confers gemcitabine resistance in pancreatic cancer via mir 491 5p snail socs3 axis |
| url | http://dx.doi.org/10.1155/2023/6510571 |
| work_keys_str_mv | AT rongxiangwu extracellularvesicleloadedoncogeniclncrnaneat1fromadiposederivedmesenchymalstemcellsconfersgemcitabineresistanceinpancreaticcancerviamir4915psnailsocs3axis AT zhansu extracellularvesicleloadedoncogeniclncrnaneat1fromadiposederivedmesenchymalstemcellsconfersgemcitabineresistanceinpancreaticcancerviamir4915psnailsocs3axis AT lezhao extracellularvesicleloadedoncogeniclncrnaneat1fromadiposederivedmesenchymalstemcellsconfersgemcitabineresistanceinpancreaticcancerviamir4915psnailsocs3axis AT ruifengpei extracellularvesicleloadedoncogeniclncrnaneat1fromadiposederivedmesenchymalstemcellsconfersgemcitabineresistanceinpancreaticcancerviamir4915psnailsocs3axis AT yirending extracellularvesicleloadedoncogeniclncrnaneat1fromadiposederivedmesenchymalstemcellsconfersgemcitabineresistanceinpancreaticcancerviamir4915psnailsocs3axis AT deqiangli extracellularvesicleloadedoncogeniclncrnaneat1fromadiposederivedmesenchymalstemcellsconfersgemcitabineresistanceinpancreaticcancerviamir4915psnailsocs3axis AT shuozhu extracellularvesicleloadedoncogeniclncrnaneat1fromadiposederivedmesenchymalstemcellsconfersgemcitabineresistanceinpancreaticcancerviamir4915psnailsocs3axis AT luxu extracellularvesicleloadedoncogeniclncrnaneat1fromadiposederivedmesenchymalstemcellsconfersgemcitabineresistanceinpancreaticcancerviamir4915psnailsocs3axis AT weizhao extracellularvesicleloadedoncogeniclncrnaneat1fromadiposederivedmesenchymalstemcellsconfersgemcitabineresistanceinpancreaticcancerviamir4915psnailsocs3axis AT wuyuanzhou extracellularvesicleloadedoncogeniclncrnaneat1fromadiposederivedmesenchymalstemcellsconfersgemcitabineresistanceinpancreaticcancerviamir4915psnailsocs3axis |