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

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

Stem Cell Research & Therapy ◽

10.1186/s13287-020-01908-z ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Feng Ding ◽

Jinhua Liu ◽

Xiaofei Zhang

Keyword(s):

Cervical Cancer ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Cancer Cells ◽

Extracellular Vesicles ◽

Cervical Cancer Cells ◽

Marrow Mesenchymal Stem Cells

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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