Cargando…
Human Mesenchymal Stem Cell-Derived Exosomal microRNA-143 Promotes Apoptosis and Suppresses Cell Growth in Pancreatic Cancer via Target Gene Regulation
BACKGROUND: This study aimed to explore the regulatory mechanism of hsa-miR-143-3p and lncRNA RP11-363N22.3–functioning upstream of KRAS–in exosomes derived from human mesenchymal stem cells (hMSCs) in pancreatic cancer. METHODS: Western blotting and quantitative PCR were used to determine gene expr...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907650/ https://www.ncbi.nlm.nih.gov/pubmed/33643376 http://dx.doi.org/10.3389/fgene.2021.581694 |
_version_ | 1783655543472128000 |
---|---|
author | Wang, Bingyi Xu, Yan Wei, Yuhua Lv, Lixin Liu, Nanbin Lin, Rui Wang, Xiuyan Shi, Baomin |
author_facet | Wang, Bingyi Xu, Yan Wei, Yuhua Lv, Lixin Liu, Nanbin Lin, Rui Wang, Xiuyan Shi, Baomin |
author_sort | Wang, Bingyi |
collection | PubMed |
description | BACKGROUND: This study aimed to explore the regulatory mechanism of hsa-miR-143-3p and lncRNA RP11-363N22.3–functioning upstream of KRAS–in exosomes derived from human mesenchymal stem cells (hMSCs) in pancreatic cancer. METHODS: Western blotting and quantitative PCR were used to determine gene expression. In vitro, cell proliferation, apoptosis, and cell cycle and invasion were evaluated using CCK-8 assay, flow cytometry, and transwell assays, respectively. In vivo, the effect of hsa-miR143-3p was investigated using a tumorigenesis test in nude mice. The association between hsa-miR-143-3p and lncRNA RP11-363N22.3 was investigated using the dual-luciferase assay. RESULTS: hsa-miR-143-3p expression significantly increased in hMSC exosomes than in those in human pancreatic cancer cell line (CFPAC-1) exosomes. In vitro, compared to the MOCK (CFPAC-1 only) group, cell proliferation and invasion were inhibited and apoptosis was induced in the inhibitor NC (CFPAC-1 + MSC-hsa-miR-3p inhibitor NC) group, while these changes were reversed in the inhibitor (CFPAC-1 + MSC-hsa-miR-3p inhibitor) group. The expression of lncRNA RP11-363N22.3 and genes related to miR-143 significantly decreased in the inhibitor NC group compared to the MOCK group, and increased in the inhibitor group compared to inhibitor NC group. A targeted combinatorial effect was observed between lncRNA RP11-363N22.3 and hsa-miR-143-3p. In vivo, the tumor volume of the mimics (CFPAC-1 + MSC-hsa-miR-143-3p mimics) group was smaller than that of the mimics NC (CFPAC-1 + MSC-hsa-miR-143-3p mimics NC) and MOCK groups. H&E staining showed that there were no obvious pathological changes in MOCK and mimic NC groups, while cell necrosis was seen in some regions in mimic groups. CONCLUSION: hsa-miR-143-3p may promote apoptosis and suppress cell growth and invasion in pancreatic cancer. |
format | Online Article Text |
id | pubmed-7907650 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79076502021-02-27 Human Mesenchymal Stem Cell-Derived Exosomal microRNA-143 Promotes Apoptosis and Suppresses Cell Growth in Pancreatic Cancer via Target Gene Regulation Wang, Bingyi Xu, Yan Wei, Yuhua Lv, Lixin Liu, Nanbin Lin, Rui Wang, Xiuyan Shi, Baomin Front Genet Genetics BACKGROUND: This study aimed to explore the regulatory mechanism of hsa-miR-143-3p and lncRNA RP11-363N22.3–functioning upstream of KRAS–in exosomes derived from human mesenchymal stem cells (hMSCs) in pancreatic cancer. METHODS: Western blotting and quantitative PCR were used to determine gene expression. In vitro, cell proliferation, apoptosis, and cell cycle and invasion were evaluated using CCK-8 assay, flow cytometry, and transwell assays, respectively. In vivo, the effect of hsa-miR143-3p was investigated using a tumorigenesis test in nude mice. The association between hsa-miR-143-3p and lncRNA RP11-363N22.3 was investigated using the dual-luciferase assay. RESULTS: hsa-miR-143-3p expression significantly increased in hMSC exosomes than in those in human pancreatic cancer cell line (CFPAC-1) exosomes. In vitro, compared to the MOCK (CFPAC-1 only) group, cell proliferation and invasion were inhibited and apoptosis was induced in the inhibitor NC (CFPAC-1 + MSC-hsa-miR-3p inhibitor NC) group, while these changes were reversed in the inhibitor (CFPAC-1 + MSC-hsa-miR-3p inhibitor) group. The expression of lncRNA RP11-363N22.3 and genes related to miR-143 significantly decreased in the inhibitor NC group compared to the MOCK group, and increased in the inhibitor group compared to inhibitor NC group. A targeted combinatorial effect was observed between lncRNA RP11-363N22.3 and hsa-miR-143-3p. In vivo, the tumor volume of the mimics (CFPAC-1 + MSC-hsa-miR-143-3p mimics) group was smaller than that of the mimics NC (CFPAC-1 + MSC-hsa-miR-143-3p mimics NC) and MOCK groups. H&E staining showed that there were no obvious pathological changes in MOCK and mimic NC groups, while cell necrosis was seen in some regions in mimic groups. CONCLUSION: hsa-miR-143-3p may promote apoptosis and suppress cell growth and invasion in pancreatic cancer. Frontiers Media S.A. 2021-02-12 /pmc/articles/PMC7907650/ /pubmed/33643376 http://dx.doi.org/10.3389/fgene.2021.581694 Text en Copyright © 2021 Wang, Xu, Wei, Lv, Liu, Lin, Wang and Shi. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Wang, Bingyi Xu, Yan Wei, Yuhua Lv, Lixin Liu, Nanbin Lin, Rui Wang, Xiuyan Shi, Baomin Human Mesenchymal Stem Cell-Derived Exosomal microRNA-143 Promotes Apoptosis and Suppresses Cell Growth in Pancreatic Cancer via Target Gene Regulation |
title | Human Mesenchymal Stem Cell-Derived Exosomal microRNA-143 Promotes Apoptosis and Suppresses Cell Growth in Pancreatic Cancer via Target Gene Regulation |
title_full | Human Mesenchymal Stem Cell-Derived Exosomal microRNA-143 Promotes Apoptosis and Suppresses Cell Growth in Pancreatic Cancer via Target Gene Regulation |
title_fullStr | Human Mesenchymal Stem Cell-Derived Exosomal microRNA-143 Promotes Apoptosis and Suppresses Cell Growth in Pancreatic Cancer via Target Gene Regulation |
title_full_unstemmed | Human Mesenchymal Stem Cell-Derived Exosomal microRNA-143 Promotes Apoptosis and Suppresses Cell Growth in Pancreatic Cancer via Target Gene Regulation |
title_short | Human Mesenchymal Stem Cell-Derived Exosomal microRNA-143 Promotes Apoptosis and Suppresses Cell Growth in Pancreatic Cancer via Target Gene Regulation |
title_sort | human mesenchymal stem cell-derived exosomal microrna-143 promotes apoptosis and suppresses cell growth in pancreatic cancer via target gene regulation |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907650/ https://www.ncbi.nlm.nih.gov/pubmed/33643376 http://dx.doi.org/10.3389/fgene.2021.581694 |
work_keys_str_mv | AT wangbingyi humanmesenchymalstemcellderivedexosomalmicrorna143promotesapoptosisandsuppressescellgrowthinpancreaticcancerviatargetgeneregulation AT xuyan humanmesenchymalstemcellderivedexosomalmicrorna143promotesapoptosisandsuppressescellgrowthinpancreaticcancerviatargetgeneregulation AT weiyuhua humanmesenchymalstemcellderivedexosomalmicrorna143promotesapoptosisandsuppressescellgrowthinpancreaticcancerviatargetgeneregulation AT lvlixin humanmesenchymalstemcellderivedexosomalmicrorna143promotesapoptosisandsuppressescellgrowthinpancreaticcancerviatargetgeneregulation AT liunanbin humanmesenchymalstemcellderivedexosomalmicrorna143promotesapoptosisandsuppressescellgrowthinpancreaticcancerviatargetgeneregulation AT linrui humanmesenchymalstemcellderivedexosomalmicrorna143promotesapoptosisandsuppressescellgrowthinpancreaticcancerviatargetgeneregulation AT wangxiuyan humanmesenchymalstemcellderivedexosomalmicrorna143promotesapoptosisandsuppressescellgrowthinpancreaticcancerviatargetgeneregulation AT shibaomin humanmesenchymalstemcellderivedexosomalmicrorna143promotesapoptosisandsuppressescellgrowthinpancreaticcancerviatargetgeneregulation |