Department of Functional Examination, Qingdao Sixth People's Hospital, Qingdao 266003, Shangdong, China.
Department of Ninth Liver Disease, Qingdao Sixth People's Hospital, Qingdao 266003, Shangdong, China.
Anal Cell Pathol (Amst). 2022 Jan 27;2022:9302496. doi: 10.1155/2022/9302496. eCollection 2022.
Nowadays, microRNA-375 (miR-375) has been implicated in many types of cancers, including hepatocellular carcinoma (HCC), and the functions of miRNAs encapsulated by extracellular vesicles (EV) in HCC progression have also been extensively investigated. In this research, we aimed to probe into the mechanism of EV-encapsulated miR-375 from bone marrow-derived mesenchymal stem cells (BM-MSCs) in HCC progression. At first, miR-375 expression in HCC tissues and cells was detected using RT-qPCR, and miR-375 was overexpressed to specify the effects of miR-375 on the malignant phenotype of HCC cells. miR-375 was downregulated in HCC, and overexpression of miR-375 suppressed HCC cell growth. Then, BM-MSCs and EV were isolated and identified, and, EV were cocultured with HCC cells for further functional assays. It was found that miR-375 encapsulated by EV could restrict the malignant phenotypes of HCC cells. Furthermore, the downstream genes and signaling cascades involved in HCC growth were investigated. HOXB3 was determined to be a downstream target of miR-375, and upregulation of miR-375 decreased Wnt1 and -catenin protein expression. Furthermore, HOXB3 blocked the repressive effects of miR-375 on HCC cells and Wnt1 and -catenin expression. This study highlights that miR-375 encapsulated by EV inhibits HCC development via modulating the HOXB3/Wnt/-catenin axis.
如今，microRNA-375（miR-375）已被涉及到多种癌症中，包括肝细胞癌（HCC），并且细胞外囊泡（EV）包裹的 miRNA 在 HCC 进展中的功能也得到了广泛研究。在这项研究中，我们旨在探讨骨髓间充质干细胞（BM-MSCs）来源的 EV 中包裹的 miR-375 在 HCC 进展中的作用机制。首先，通过 RT-qPCR 检测 HCC 组织和细胞中的 miR-375 表达，并过表达 miR-375 以确定 miR-375 对 HCC 细胞恶性表型的影响。miR-375 在 HCC 中下调，过表达 miR-375 抑制 HCC 细胞生长。然后，分离和鉴定 BM-MSCs 和 EV，并将 EV 与 HCC 细胞共培养进行进一步的功能测定。结果发现，EV 包裹的 miR-375 可以抑制 HCC 细胞的恶性表型。此外，还研究了涉及 HCC 生长的下游基因和信号通路。HOXB3 被确定为 miR-375 的下游靶基因，上调 miR-375 降低了 Wnt1 和 -catenin 蛋白表达。此外，HOXB3 阻断了 miR-375 对 HCC 细胞和 Wnt1 和 -catenin 表达的抑制作用。本研究强调了 EV 包裹的 miR-375 通过调节 HOXB3/Wnt/-catenin 轴抑制 HCC 发展。
