microRNA-375 released from extracellular vesicles of bone marrow mesenchymal stem cells exerts anti-oncogenic effects against cervical cancer

Abstract Background Cervical cancer is the most prevalent gynecological malignancies accompanied by high mortality, where finding a more effective therapeutic option for cervical cancer is necessary. The inhibitory role of microRNAs (miRNAs) derived from the extracellular vesicles (EVs) of the bone marrow mesenchymal stem cells (BMSCs) was analyzed in cervical cancer. Methods Expression of miR-375 was examined by RT-qPCR in cervical cancer cell lines. The targeting relation between miR-375 and maternal embryonic leucine zipper kinase (MELK) was predicted by bioinformatics analysis and verified by dual-luciferase reporter gene assay. Isolated BMSCs were transfected with lentivirus-mediated vectors, followed by EV extraction. The morphology of EVs was then identified using a NanoSight particle size analyzer and transmission electron microscope (TEM). The biological properties of cervical cancer cells were evaluated using Transwell, EdU, and TUNEL assays, respectively. Xenograft tumors in nude mice were observed to assess cervical tumorigenesis in vivo. Results Low expression of miR-375 and high expression of MELK were detected in cervical cancer samples. MELK was identified as the target gene of miR-375, which was negatively correlated with miR-375 levels. Overexpression of miR-375 suppressed proliferation, migration, and invasion of cervical cancer cells, but enhanced cell apoptosis by cooperating with downregulated MELK expression. miR-375 transferred from BMSC-derived EVs exerted the same effects on cell biological activities. Xenograft assays in vivo proved that miR-375 from BMSC-derived EVs inhibited tumor growth. Conclusion The present study highlighted the role of miR-375 from BMSC-derived EVs in suppressing the progression of cervical cancer, which may contribute to the discovery of novel potential biomarkers for cervical cancer therapy.

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LncRNA Neu Mediates Bone Marrow Mesenchymal Stem Cells (BMSCs) Growth and Promotes Cervical Cancer Progression Through Suppression of MicroRNA-625

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2956 ◽

2022 ◽

Vol 12 (4) ◽

pp. 862-866

Author(s):

Qiuxiang Ning ◽

Fa Guo ◽

Pengfei Xiao ◽

Xiulan Liu ◽

Ya Ding

Keyword(s):

Cervical Cancer ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Cell Viability ◽

Cancer Progression ◽

Pearson Correlation ◽

Marrow Mesenchymal Stem Cells ◽

After Cancer

The tumorigenesis mechanism of cervical cancer (CC) is complicated as several pathways deserve exploration. LncRNAs are recently highlighted to be involved in various biological processes. The role of bone marrow mesenchymal stem cells (BMSCs) in tumor regulation is recently investigated. Herein, we aimed to explore the interaction between lncRNA Neu and microRNA (miR)-625 and BMSCs in CC. Expression levels of lncRNA Neu and miR-625 in CC cells and BMSCs were determined by RT-qPCR. The relationship between lncRNA Neu and miR-625 was analyzed by Pearson correlation analysis. After cancer cells were transfected with siRNA-Neu, CCK-8 assay and clone formation assay were conducted to determine cell proliferation and viability. LncRNA Neu was highly expressed in CC cells and poorly expressed in BMSCs. Knockdown of lncRNA Neu attenuated cell viability and proliferation while increased miR-625 expression. MiR-625 expression was negatively correlated with expression of lncRNA Neu in CC cells. Overexpression of miR-625 resulted in weakened CC cell viability. Collectively, lncRNA Neu was highly expressed in CC and promoted the development of CC through stimulating the growth of BMSCs and suppressing miR-625 expression. These findings provide a novel insight into targeted therapy for CC.

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Role of interleukin‐7 in fusion of rat bone marrow mesenchymal stem cells with cardiomyocytes in vitro and improvement of cardiac function in vivo

Cardiovascular Therapeutics ◽

10.1111/1755-5922.12479 ◽

2018 ◽

Vol 36 (6) ◽

pp. e12479 ◽

Cited By ~ 3

Author(s):

Kanwal Haneef ◽

Anwar Ali ◽

Irfan Khan ◽

Nadia Naeem ◽

Siddiqua Jamall ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Cardiac Function ◽

Interleukin 7 ◽

Marrow Mesenchymal Stem Cells ◽

Rat Bone

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Role of microRNA-335 carried by bone marrow mesenchymal stem cells-derived extracellular vesicles in bone fracture recovery

Cell Death and Disease ◽

10.1038/s41419-021-03430-3 ◽

2021 ◽

Vol 12 (2) ◽

Author(s):

Haifeng Hu ◽

Dong Wang ◽

Lihong Li ◽

Haiyang Yin ◽

Guoyu He ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Extracellular Vesicles ◽

Bone Fracture ◽

Osteoblast Differentiation ◽

Healing Time ◽

Marrow Mesenchymal Stem Cells ◽

Fracture Models

AbstractMesenchymal stem cells (MSCs) have the potential to reduce healing time and treat nonunion in fracture patients. In this study, bone marrow MSCs-derived extracellular vesicles (B-EVs) were firstly extracted and identified. CD9−/− and normal mice were enrolled for the establishment of fracture models and then injected with B-EVs. Osteoblast differentiation and fracture recovery were estimated. The levels of osteoblast-related genes were detected, and differentially expressed microRNAs (miRs) in B-EVs-treated normal fracture mice were screened and verified. The downstream mechanisms of miR were predicted and assessed. The loss-of functions of miR-335 in B-EV and gain-of-functions of VapB were performed in animal and cell experiments to evaluate their roles in bone fracture. Collectively, B-EVs promoted bone fracture recovery and osteoblast differentiation by releasing miR-335. miR-335 downregulation in B-EVs impaired B-EV functions in fracture recovery and osteoblast differentiation. miR-335 could target VapB, and VapB overexpression reversed the effects of B-EVs on osteoblast differentiation. B-EV treatment activated the Wnt/β-catenin pathway in fracture mice and osteoblasts-like cells. Taken together, the study suggested that B-EVs carry miR-335 to promote bone fracture recovery via VapB and the Wnt/β-catenin pathway. This study may offer insights into bone fracture treatment.

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The Regulatory Effect of miR-126-3p Exosomes Derived from Bone Marrow Mesenchymal Stem Cells (BMSCs) Targeting Endothelial Cell Specific Molecule 1 on Gastric Cancer

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2843 ◽

2021 ◽

Vol 11 (12) ◽

pp. 2415-2420

Author(s):

Sujuan Wu ◽

Jinyan Wang ◽

Tao Niu

Keyword(s):

Gastric Cancer ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Cancer Cells ◽

Gastric Cancer Cells ◽

Gene Reporter Assay ◽

Marrow Mesenchymal Stem Cells ◽

Other Substances

Exosomes can transmit microRNAs (miRNAs) and other substances between different cells. Bone marrow mesenchymal stem cells (BMSCs) can migrate to tumor sites. They are related to a variety of tumors, but the role of miR-126-3p exosomes derived from BMSCs in gastric cancer has not been elucidated. miR-126-3p overexpressing BMSCs were established and cell supernatant exosomes were collected followed by measuring miR-126-3p level by PCR, ESM1 expression by western blot, targeting relationship by dual luciferase gene reporter assay along with analysis of cell proliferation, invasion and apoptosis. The addition of BMSCs exosomes to gastric cancer cells reduced the miR-126-3p level, promoted ESM1 expression, and worsened the biological behaviors of tumor cells. miR-126-3p-overexpressed BMSCs exosomes promoted miR-126-3p expression, resulting in the decrease of ESM1 expression and inhibiting the further deterioration. In conclusion, BMSCs can inhibit the increase of miR-126-3p expression and ESM1 to inhibit the deterioration of biological behaviors of gastric cancer cells.

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The potential oncogenic and MLN4924-resistant effects of CSN5 on cervical cancer cells

Cancer Cell International ◽

10.1186/s12935-021-02078-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Huilin Zhang ◽

Ping He ◽

Qing Zhou ◽

Yan Lu ◽

Bingjian Lu

Keyword(s):

Cell Cycle ◽

Cervical Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cancer Cell ◽

Cervical Cancer Cell ◽

Cervical Cancers ◽

Cervical Cancer Cells

Abstract Background CSN5, a member of Cop9 signalosome, is essential for protein neddylation. It has been supposed to serve as an oncogene in some cancers. However, the role of CSN5 has not been investigated in cervical cancer yet. Methods Data from TCGA cohorts and GEO dataset was analyzed to examine the expression profile of CSN5 and clinical relevance in cervical cancers. The role of CSN5 on cervical cancer cell proliferation was investigated in cervical cancer cell lines, Siha and Hela, through CSN5 knockdown via CRISPR–CAS9. Western blot was used to detect the effect of CSN5 knockdown and overexpression. The biological behaviors were analyzed by CCK8, clone formation assay, 3-D spheroid generation assay and cell cycle assay. Besides, the role CSN5 knockdown in vivo was evaluated by xenograft tumor model. MLN4924 was given in Siha and Hela with CSN5 overexpression. Results We found that downregulation of CSN5 in Siha and Hela cells inhibited cell proliferation in vitro and in vivo, and the inhibitory effects were largely rescued by CSN5 overexpression. Moreover, deletion of CSN5 caused cell cycle arrest rather than inducing apoptosis. Importantly, CSN5 overexpression confers resistance to the anti-cancer effects of MLN4924 (pevonedistat) in cervical cancer cells. Conclusions Our findings demonstrated that CSN5 functions as an oncogene in cervical cancers and may serve as a potential indicator for predicting the effects of MLN4924 treatment in the future.

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Bone marrow mesenchymal stem cells-derived extracellular vesicles carrying microRNA-221-3p protect against ischemic stroke via ATF3

Brain Research Bulletin ◽

10.1016/j.brainresbull.2021.04.022 ◽

2021 ◽

Author(s):

Zhibing Ai ◽

Chaohui Cheng ◽

Lan Zhou ◽

Songhe Yin ◽

Lei Wang ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Ischemic Stroke ◽

Extracellular Vesicles ◽

Marrow Mesenchymal Stem Cells

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Exosomal MicroRNA-204 Derived from Bone Marrow Mesenchymal Stem Cells (BMSCs) Inhibits Cell Proliferation and Induces Apoptosis Through NF-κB Signaling Pathway in Breast Cancer

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2900 ◽

2022 ◽

Vol 12 (2) ◽

pp. 273-278

Author(s):

Daqing Jiang ◽

Xianxin Xie ◽

Cong Wang ◽

Weijie Li ◽

Jianjun He

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Bone Marrow ◽

Cell Proliferation ◽

Mesenchymal Stem Cells ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Marrow Mesenchymal Stem Cells ◽

Induced Apoptosis ◽

Signaling Activation

Our study intends to assess the relationship between exosomes derived from bone marrow mesenchymal stem cells (BMSC-exo) and breast cancer. BMSC-exo were isolated and characterized by transmission electron microscopy. After transfection of BMSCs with miR-204 inhibitor, breast cancer cells were incubated with BMSC-exo followed by analysis of cell proliferation by CCK-8 assay, cell apoptosis by flow cytometry, and expression of apoptosis-related protein and NF-κB signaling by western blot. The co-culture of BMSC-exo with breast cancer cells enhanced miR-204 transcription, inhibited cell proliferation and induced apoptosis. Further, BMSC-exo accelerated apoptosis as demonstrated by the increased level of Bax and casepase-3 and decreased Bcl-2 expression, as well as reduced NF-κB signaling activity. But knockdown of miR-204 abolished the effect of BMSC-exo on apoptosis and proliferation with NF-κB signaling activation. In conclusion, miR-204 from BMSC-exo restrains growth of breast cancer cell and might be a novel target for treating breast cancer.

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