Dataset Information

Exosomes from BM-MSCs increase the population of CSCs via transfer of miR-142-3p.

ABSTRACT:

Background

Bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) are progenitor cells shown to migrate to the tumour and participate in the tumour microenvironment. BM-MSCs play important roles in tumour processes through the release of cytokines or exosomes; however, how BM-MSCs influence the stemness of CSCs in colon cancer cells remains poorly understood.

Methods

We isolated exosomes from BM-MSCs and used these exosomes to treat colon cancer cells (HCT-116, HT-29 and SW-480). We compared stemness traits of colon CSCs by cell surface marker (CD133 and Lgr5) and functional assays, such as chemoresistance, colony formation, cell adhesion, invasion and tumour-formation assay. We performed a microRNA array to investigate the differences in exosomal microRNA expression between colon cancer cells, BM-MSCs and co-cultured cells and performed functional and molecular analysis of the gene targets.

Results

In this study, we found that BM-MSC-derived exosomes contained distinct microRNAs, including miR-142-3p, which in turn increased the population of CSCs in colon cancer cells. Depriving miR-142-3p from BM-MSC-derived exosomes clearly decreased the population of colon CSCs. Mechanistically, Numb was found to be the target gene of miR-142-3p, and miR-142-3p promoted the Notch signalling pathway by downregulating Numb.

Conclusions

Our findings indicate that BM-MSC-derived exosomes promote colon cancer stem cell-like traits via miR-142-3p.

SUBMITTER: Li H

PROVIDER: S-EPMC6173771 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Radiotherapy to cancer patients is inevitably accompanied by normal tissue injury, and the bone is one of the most commonly damaged tissues. Damage to bone marrow mesenchymal stem cells (BM-MSCs) induced by radiation is thought to be a major cause of radiation-induced bone loss. Exosomes exhibit great therapeutic potential in the treatment of osteoporosis, but whether exosomes are involved in radiation-induced bone loss has not been thoroughly elucidated to date. The main purpose of this study is to investigate the role of exosomes derived from BM-MSCs in restoring recipient BM-MSC function and alleviating radiation-induced bone loss. METHODS:BM-MSC-derived exosomes were intravenously injected to rats immediately after irradiation. After 28?days, the left tibiae were harvested for micro-CT and histomorphometric analysis. The effects of exosomes on antioxidant capacity, DNA damage repair, proliferation, and cell senescence of recipient BM-MSCs were determined. Osteogenic and adipogenic differentiation assays were used to detect the effects of exosomes on the differentiation potential of recipient BM-MSCs, and related genes were measured by qRT-PCR and Western blot analysis. ?-Catenin expression was detected at histological and cytological levels. RESULTS:BM-MSC-derived exosomes can attenuate radiation-induced bone loss in a rat model that is similar to mesenchymal stem cell transplantation. Exosome-treated BM-MSCs exhibit reduced oxidative stress, accelerated DNA damage repair, and reduced proliferation inhibition and cell senescence-associate protein expression compared with BM-MSCs that exclusively received irradiation. Following irradiation, exosomes promote ?-catenin expression in BM-MSCs and restore the balance between adipogenic and osteogenic differentiation. CONCLUSIONS:Our findings indicate that BM-MSC-derived exosomes take effects by restoring the function of recipient BM-MSCs. Therefore, exosomes may represent a promising cell-free therapeutic approach for the treatment of radiation-induced bone loss.