Exosomal miRNA‐1231 derived from bone marrow mesenchymal stem cells inhibits the activity of pancreatic cancer

Abstract

Pancreatic cancer (PC) is a highly malignant tumor with increased morbidity and mortality, which is difficult to diagnose and cure in the clinic. Through secreting exosomes containing biological molecules, including diverse RNAs and proteins, bone marrow mesenchymal stem cells (BM‐MSCs) influence the immunity, inflammation, tumor environment, and cancer metastasis. In this study, low expression of miRNA‐1231 (miR‐1231) in exosomes derived from the peripheral blood was significantly correlated with the TNM stage of PC, suggesting the potential inhibitory effect of exosomal miR‐1231 on PC occurrence and development. The proliferation, migration, invasion, and adhesion to the matrix of PC cells BxPC‐3 and PANC‐1 were negatively regulated by exosomes derived from the supernatants of BM‐MSCs that transfected with miR‐1231 oligonucleotides. Simultaneously, tumor growth in vivo was seriously restrained in BALB/C nude mice by tail vein injection with exosomes originated from BM‐MSCs that transfected with miR‐1231 mimics. The exosomes extracted from BM‐MSCs with high level of miR‐1231 inhibit the activity of PC, providing the potential application for developing new and efficient medicine for cancer therapy, especially for PC treatment. The exosomal miR‐1231 of peripheral blood may also be a potential indicator for PC diagnosis in the future.

Low miR-1231 expression predicts poor prognosis in non-small cell lung cancer and accelerates cell proliferation, migration and invasion

“…MiR-1231 expression was downregulated in prostate cancer and may suppress prostate cancer cell proliferation, migration and invasion by targeting EGFR (28). Exosomal miR-1231 inhibit the expression of pancreatic cancer (29,30). The upregulated miR-1231 was found in colorectal cancer, which may be related to the onset of colorectal cancer (31).…”

Mechanical loading stimulates bone angiogenesis through enhancing type H vessel formation and downregulating exosomal miR‐214‐3p from bone marrow‐derived mesenchymal stem cells

“…The culture medium of BMMSCs was replaced with an exosome‐free medium supplemented with 10% FBS, 100 U/mL of penicillin, and 100 μg/mL of streptomycin. Forty‐eight hours after transfection, HUVECs became ready for the following experiments and exosome‐free medium of BMMSCs was be collected for exosomes 44 …”

“…Forty-eight hours after transfection, HUVECs became ready for the following experiments and exosome-free medium of BMMSCs was be collected for exosomes. 44…”

Dual Role of MSC-Derived Exosomes in Tumor Development

“…Similarly, exosomal miR-222/223 was confirmed to stimulate cycling quiescence and early breast cancer dormancy in the bone marrow [ 60 ]. In addition, Shang et al found that MSC-derived exosomal miRNA-1231 inhibits the activity of pancreatic cancer [ 61 ], and Liu et al [ 62 ] demonstrated that MSC-derived exosomes enhance imatinib-induced apoptosis in human leukemia cells through activation of the caspase signaling pathway.…”