Abstract
Objective Exosomes (exo) which contain proteins, microRNAs (miRNAs), and other bioactive substances can participate in intercellular signal transduction and material transport. Bone marrow mesenchymal stem cells (BMSCs) have a strong ability to produce exosomes. The purpose of this study was to observe the effect of hBMSCs-derived-exo miR-22-3p on proliferation and invasion of colorectal cancer (CRC) cells and to explore its mechanism. Methods miR-22-3p and RAS oncogene family (RAP2B) expression was detected using qRT-PCR or Western blotting. Their interaction was confirmed by dual luciferase activity assay. Effects of miR-22-3p on cell proliferation and invasion were evaluated by CCK-8 and Transwell assay, respectively. Exosomes were extracted by the ultracentrifugation and identified through electron microscopy and Western blotting. Results In CRC tissues and cells, downregulation of miR-22-3p and upregulation of RAP2B were observed. According to the analysis of dual luciferase activity, RAP2B was a target gene of miR-22-3p. In addition, miR-22-3p obviously repressed the cells proliferation and invasion via mediating RAP2B/PI3K/AKT pathway. Coculture experiments indicated that miR-22-3p derived from hBMSCs-exo had inhibition effects on SW480 cell proliferation and invasion. Conclusions Collectively, miR-22-3p from hBMSCs-exo might impede CRC progression, which emphasized the potential of hBMSCs-exo-miR-22-3p as CRC treatment in the future.
Highlights
Colorectal cancer (CRC) is one of the common malignant tumors of the digestive tract with higher global morbidity and mortality [1]
NCM460 cells, human CRC cell lines (HT-29, SW620, HCT-116, SW480, and LoVo), and hBMSCs were purchased from American Type Culture Collection (MD, USA). hBMSCs were cultured in DMEM/F12 (supplemented with 10% fetal bovine serum (FBS, Gibco, USA)) and 1% penicillin-streptomycin) medium (Gibco, USA)
According to TargetScan online software analysis, we found that RAP2B may be one of the important target genes regulated by miR-22-3p. miR-22-3p can complementarily bind to the 3’ UTR region of RAP2B (Figure 3(a)). e detection of luciferase activity revealed that miR-22-3p overexpression obviously reduced luciferase activity in the RAP2B-wt group but had no significant effect on the RAP2B-mut group (Figure 3(b)). is showed that miR-22-3p could bind to RAP2B
Summary
Exosomes (exo) which contain proteins, microRNAs (miRNAs), and other bioactive substances can participate in intercellular signal transduction and material transport. E purpose of this study was to observe the effect of hBMSCs-derived-exo miR-22-3p on proliferation and invasion of colorectal cancer (CRC) cells and to explore its mechanism. MiR-22-3p and RAS oncogene family (RAP2B) expression was detected using qRT-PCR or Western blotting. Eir interaction was confirmed by dual luciferase activity assay. Effects of miR-22-3p on cell proliferation and invasion were evaluated by CCK-8 and Transwell assay, respectively. Exosomes were extracted by the ultracentrifugation and identified through electron microscopy and Western blotting. In CRC tissues and cells, downregulation of miR-22-3p and upregulation of RAP2B were observed. According to the analysis of dual luciferase activity, RAP2B was a target gene of miR-22-3p. MiR-22-3p obviously repressed the cells proliferation and invasion via mediating RAP2B/PI3K/AKT pathway. Coculture experiments indicated that miR-22-3p derived from hBMSCs-exo had inhibition effects on SW480 cell proliferation and invasion. MiR-22-3p from hBMSCs-exo might impede CRC progression, which emphasized the potential of hBMSCs-exo-miR-22-3p as CRC treatment in the future
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