Human Mesenchymal Stem Cell-Derived Exosomal microRNA-143 Promotes Apoptosis and Suppresses Cell Growth in Pancreatic Cancer via Target Gene Regulation

This study aimed to explore the regulatory mechanism of hsa-miR-143-3p and lncRNA RP11-363N22.3-functioning upstream of -in exosomes derived from human mesenchymal stem cells (hMSCs) in pancreatic cancer. Western blotting and quantitative PCR were used to determine gene expression. , cell proliferat...

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Veröffentlicht in:Frontiers in genetics 2021-02, Vol.12, p.581694-581694
Hauptverfasser: Wang, Bingyi, Xu, Yan, Wei, Yuhua, Lv, Lixin, Liu, Nanbin, Lin, Rui, Wang, Xiuyan, Shi, Baomin
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Sprache:eng
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Zusammenfassung:This study aimed to explore the regulatory mechanism of hsa-miR-143-3p and lncRNA RP11-363N22.3-functioning upstream of -in exosomes derived from human mesenchymal stem cells (hMSCs) in pancreatic cancer. Western blotting and quantitative PCR were used to determine gene expression. , cell proliferation, apoptosis, and cell cycle and invasion were evaluated using CCK-8 assay, flow cytometry, and transwell assays, respectively. , 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. hsa-miR-143-3p expression significantly increased in hMSC exosomes than in those in human pancreatic cancer cell line (CFPAC-1) exosomes. , 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. , 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. hsa-miR-143-3p may promote apoptosis and suppress cell growth and invasion in pancreatic cancer.
ISSN:1664-8021
1664-8021
DOI:10.3389/fgene.2021.581694