Abstract
BackgroundThis 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.MethodsWestern 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.Resultshsa-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.Conclusionhsa-miR-143-3p may promote apoptosis and suppress cell growth and invasion in pancreatic cancer.
Highlights
Pancreatic cancer has extremely poor prognosis and is the fifth leading cause of cancer-related deaths (Reis et al, 2017)
CD63 and HSP70 are regarded as detection markers for exosomes, which have been found in both CFPAC-1 and human mesenchymal stem cells (hMSCs) exosomes (Figure 1D)
The results showed that U6 expression between CFPAC-1 and hMSC exosomes was significantly different (p < 0.001), while hsa-miR494-3p was stably expressed without significant differences in both CFPAC-1 and hMSC exosomes (p > 0.05), hsa-miR494-3p was selected as the internal control
Summary
Pancreatic cancer has extremely poor prognosis and is the fifth leading cause of cancer-related deaths (Reis et al, 2017). The common risk factors include smoking, specific inherited genetic syndromes, and a family history of pancreatic cancer (Thomas, 2017). The 5-year survival rate of pancreatic cancer is only 3–5%, and its incidence is increasing in several countries (Timofte et al, 2014). Chemotherapy has emerged as one of the primary therapeutic modalities for pancreatic cancer, the low curative rate limits its clinical application (Meng et al, 2017). Extensive studies are necessary to discover more effective treatments for pancreatic cancer. This study aimed to explore the regulatory mechanism of hsa-miR-1433p and lncRNA RP11-363N22.3–functioning upstream of KRAS–in exosomes derived from human mesenchymal stem cells (hMSCs) in pancreatic cancer
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