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人脐带间充质干细胞来源的外泌体携带 microRNA-15a-5p 通过调节 septin 2 对肾母细胞瘤发挥治疗作用。

Human umbilical cord-mesenchymal stem cells-derived exosomes carrying microRNA-15a-5p possess therapeutic effects on Wilms tumor via regulating septin 2.

机构信息

Department of Pediatric Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou City, Fujian Province, China.

Department of Gynecological, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou City, Fujian Province, China.

出版信息

Bioengineered. 2022 Mar;13(3):6136-6149. doi: 10.1080/21655979.2022.2037379.

Abstract

The exact mechanism of miR-15a-5p shuttled by human umbilical cord-mesenchymal stem cell-derived exosomes (hUC-MSCs-Exo) in Wilms tumor (WT) was estimated. WT tissues were collected clinically. miR-15a-5p and septin 2 (SEPT2) expression levels were examined in tissues . hUC-MSCs-Exo were transfected with miR-15a-5p-related oligonucleotides and co-cultured with WT cells (G-401). In addition, SEPT2 loss-of-function was performed in G-401 cells. The biological functions of G-401 cells after treatments were evaluated. Moreover, tumor formation tests further assessed the role of exosomal miR-15a-5p in WT. The miR-15a-5p level was lower and the SEPT2 level was higher in WT. hUC-MSCs-Exo impaired the biological functions of G-401 cells. hUC-MSCs-Exo carried upregulated miR-15a-5p into G-401 cells, thereby lessening the tumorigenic properties of G-401 cells. Inhibition of SEPT2 suppressed the biological function of WT cells and upregulated SEPT2 reversed hUC-MSCs-Exo-mediated inhibition of G-401 cell growth. The tumorigenicity of G-401 cells in mice was impaired by hUC-MSCs-Exo overexpressing miR-15a-5p. The data prove that miR-15a-5p shuttled by hUC-MSCs-Exo negatively regulates SEPT2 expression, and disrupts WT cell growth and .

摘要

人脐带间充质干细胞来源的外泌体(hUC-MSCs-Exo)中 miR-15a-5p 转运调控 Wilms 瘤(WT)的确切机制。临床收集 WT 组织。检测组织中 miR-15a-5p 和 septin 2(SEPT2)的表达水平。用 miR-15a-5p 相关寡核苷酸转染 hUC-MSCs-Exo 并与 WT 细胞(G-401)共培养。此外,在 G-401 细胞中进行 SEPT2 功能丧失实验。评价处理后 G-401 细胞的生物学功能。此外,肿瘤形成实验进一步评估外泌体 miR-15a-5p 在 WT 中的作用。WT 中 miR-15a-5p 水平降低,SEPT2 水平升高。hUC-MSCs-Exo 损害 G-401 细胞的生物学功能。hUC-MSCs-Exo 将上调的 miR-15a-5p 携带到 G-401 细胞中,从而降低 G-401 细胞的致瘤特性。抑制 SEPT2 可抑制 WT 细胞的生物学功能,而上调 SEPT2 可逆转 hUC-MSCs-Exo 介导的 G-401 细胞生长抑制。hUC-MSCs-Exo 过表达 miR-15a-5p 可损害 G-401 细胞在小鼠体内的致瘤性。数据证明,hUC-MSCs-Exo 转运的 miR-15a-5p 负调控 SEPT2 的表达,并破坏 WT 细胞的生长和增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c851/8973990/fa67b5cc332a/KBIE_A_2037379_UF0001_OC.jpg

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