miR-221-3p Delivered by BMMSC-Derived Microvesicles Promotes the Development of Acute Myelocytic Leukemia

Abstract

The study aims to investigate the effects of miR-221-3p in bone marrow mesenchymal stem cell (BMMSC)-derived microvesicles (MVs) on cell cycle, proliferation and invasion of acute myelocytic leukemia (AML). Methods: Bioinformatics was used to predict differentially expressed miRNAs (DEmiRNAs) in AML. The morphology of BMMSC-derived MVs was observed under an electron microscope, and the positional relation of MVs and OCI-AML2 cells was observed by a fluorescence microscope. MTT, Transwell, and flow cytometry assays were used to analyze the effects of MVs on OCI-AML2 cells. The targeted relationship between miR-221-3p and CDKN1C was detected by dual luciferase assay. Results: It was verified that miR-221-3p promoted the proliferation, invasion and migration of OCI-AML2 cells, and induced the cell cycle arrest in G1/S phase as well as inhibited cell apoptosis. Further studies showed that MVs promoted the proliferation, migration and invasion of AML, and induced the cell cycle arrest in G1/S phase through miR-221-3p. It was confirmed that miR-221-3p can directly target CDKN1C to regulate cell cycle, proliferation and invasion of AML. Conclusion: miR-221-3p in BMMSC-derived MVs regulated AML cell cycle, cell proliferation and invasion through targeting CDKN1C. miR-221-3p and CDKN1C were considered to be potential targets and biomarkers for the treatment of AML in clinic.

Exosomal miR-221-3p Derived from Bone Marrow Mesenchymal Stem Cells Alleviates Asthma Progression by Targeting FGF2 and Inhibiting the ERK1/2 Signaling Pathway

“…A large number of studies have confirmed that BMSCs-derived exosomes play crucial roles in the human pathological process through the transportation of functional miRNAs [ 7 , 21 ]. A previous study illustrated that miR-221-3p delivered by BMSCs-derived exosomes promoted the development of acute myelocytic leukemia [ 15 ]. Moreover, BMSCs-derived extracellular vesicles carrying miR-221-3p exerted a neuroprotective effect in ischemic stroke by targeting activating transcription factor 3 [ 16 ].…”

“…The decreased expression of miR-221-3p might protect against airway eosinophilic inflammation by upregulating anti-inflammatory chemokine (C-X-C motif) ligand (CXCL) 17 (CXCL17) [ 14 ]. Likewise, miR-221-3p was found to have existed in the BMSCs-derived exosomes, and miR-221-3p delivered by BMSCs-derived exosomes was found to be involved in human physiological diseases such as acute myelocytic leukemia and ischemic stroke [ 15 , 16 ]. Thus, we explored the roles of exosomal miR-221-3p derived from BMSCs in asthma progression.…”

Exosomal miR-221-3p derived from bone marrow mesenchymal stem cells alleviates asthma progression by targeting FGF2 and inhibiting the ERK1/2 signaling pathway

“…A large number of studies have con rmed BMSCs-derived exosomes play crucial roles in human pathological process through the transportation of functional miRNAs [7,17]. A previous study illustrated that miR-221-3p delivered by BMSCs-derived exosomes promotes the development of acute myelocytic leukemia [15]. Moreover, BMSCs-derived extracellular vesicles carrying microRNA-221-3p exerted neuroprotective effect in ischemic stroke by targeting activating transcription factor 3 [16].…”

“…Interestingly, the decreased expression of miR-221-3p is evidently observed in patients with asthma, implying its potential protective role in asthma progression [14]. And miR-221-3p was found to be existed in the BMSCs-derived exosomes [15,16]. Thus, we speculated that exosomal miR-221-3p derived from BMSCs may be involved in asthma progression.…”

Effects of bone marrow mesenchymal stem cells on ovarian and testicular function in aging Sprague-Dawley rats induced by D-galactose

“…These factors can promote the differentiation and proliferation of various cells, thus delaying the aging process. In addition, MSCs have been found to promote the proliferation and metastasis of head and neck cancer and leukemia cells [11,12]. Extracellular vesicles produced by MSCs can reduce microglia-mediated neuroinflammation after cortical injury in elderly Ganges macaques [13].…”