The 2nd Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, No. 71, Xinmin Street, Changchun, 130021, Jilin Province, People's Republic of China.
Mol Biotechnol. 2023 Jul;65(7):1151-1164. doi: 10.1007/s12033-022-00607-9. Epub 2022 Dec 1.
The development of cholangiocarcinoma (CCA) can be regulated by extracellular vesicles (EVs). In this study, we intend to investigate whether tumor cell-derived EVs delivering microRNA (miR)-210 affect CCA development, involved with reversion-inducing-cysteine-rich protein with kazal motifs (RECK). In silico analysis was performed for identifying differentially expressed miRs and the downstream target genes. The CCA related microarray GSE77984 was used to verify the expression of the target genes in CCA tissue samples. Targeting relationship between miR-210 and RECK was assayed. EVs were extracted from CCA cells, followed by co-culture with CCA cells. The in vitro and in vivo roles of tumor cell-derived EVs on the growth and metastasis of CCA cells were assayed. Upregulated miR-210 and downregulated RECK were found in CCA. CCA cells could uptake tumor cell-derived EVs, and the EVs could promote their migration, invasion, and chemoresistance. RECK expression could be target and inhibited by miR-210. It was further confirmed in vivo that miR-210 shuttled by tumor cell-derived EVs could specifically inhibit RECK expression, which promotes growth, metastasis and chemoresistance of CCA cells. Our current study highlighted that tumor cell-derived EVs could deliver miR-210 to CCA cells, where miR-210 specifically decreases RECK expression, which facilitates growth, metastasis and chemoresistance in CCA.
胆管癌 (CCA) 的发生发展可以受到细胞外囊泡 (EVs) 的调控。在本研究中，我们旨在研究肿瘤细胞衍生的 EV 携带 microRNA (miR)-210 是否会影响 CCA 的发生发展，其涉及到富含半胱氨酸的天冬氨酸蛋白水解酶抑制因子 (RECK)。通过计算机分析确定差异表达的 miR 和下游靶基因。使用与 CCA 组织样本相关的 microarray GSE77984 来验证靶基因的表达。检测了 miR-210 和 RECK 之间的靶向关系。从 CCA 细胞中提取 EV，然后与 CCA 细胞共培养。检测了肿瘤细胞衍生的 EV 对 CCA 细胞生长和转移的体外和体内作用。在 CCA 中发现 miR-210 上调和 RECK 下调。CCA 细胞可以摄取肿瘤细胞衍生的 EV，并且 EV 可以促进它们的迁移、侵袭和化疗耐药性。RECK 表达可以作为 miR-210 的靶基因并受到抑制。进一步在体内证实，肿瘤细胞衍生的 EV 转运的 miR-210 可以特异性抑制 RECK 的表达，从而促进 CCA 细胞的生长、转移和化疗耐药性。我们目前的研究强调了肿瘤细胞衍生的 EV 可以将 miR-210 递送到 CCA 细胞中，miR-210 特异性降低 RECK 的表达，从而促进 CCA 的生长、转移和化疗耐药性。
