Department of Pathology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China.
Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China.
World J Gastroenterol. 2020 Mar 7;26(9):933-946. doi: 10.3748/wjg.v26.i9.933.
As the most common biliary malignancy, gallbladder cancer (GC) is an elderly-biased disease. Although extensive studies have elucidated the molecular mechanism of microRNA 182 (miR-182) and reversion-inducing-cysteine-rich protein with kazal motifs (RECK) in various cancers, the specific role of exosomal miR-182 and RECK in GC remains poorly understood.
To explore the relationship between exosomal miR-182/RECK and metastasis of GC.
Paired GC and adjacent normal tissues were collected from 78 patients. Quantitative polymerase chain reaction was employed to detect miR-182 and exosomal miR-182 expression, and Western blotting was conducted to determine RECK expression. In addition, the effects of exosomal miR-182/RECK on the biological function of human GC cells were observed. Moreover, the double luciferase reporter gene assay was applied to validate the targeting relationship between miR-182 and RECK.
Compared with normal gallbladder epithelial cells, miR-182 was highly expressed in GC cells, while RECK had low expression. Exosomal miR-182 could be absorbed and transferred by cells. Exosomal miR-182 inhibited RECK expression and promoted the migration and invasion of GC cells.
Exosomal miR-182 can significantly promote the migration and invasion of GC cells by inhibiting RECK; thus miR-182 can be used as a therapeutic target for GC.
作为最常见的胆道恶性肿瘤,胆囊癌(GC)是一种老年发病为主的疾病。尽管大量研究已经阐明了 microRNA 182(miR-182)和富含半胱氨酸的 Kazal 结构域反转诱导蛋白(RECK)在各种癌症中的分子机制,但外泌体 miR-182 和 RECK 在 GC 中的具体作用仍知之甚少。
探讨外泌体 miR-182/RECK 与 GC 转移的关系。
收集 78 例患者的配对 GC 组织和相邻正常组织。采用实时定量聚合酶链反应检测 miR-182 和外泌体 miR-182 的表达,Western blot 检测 RECK 表达。此外,观察外泌体 miR-182/RECK 对人 GC 细胞生物学功能的影响。同时,应用双荧光素酶报告基因实验验证 miR-182 与 RECK 的靶向关系。
与正常胆囊上皮细胞相比,GC 细胞中 miR-182 高表达,而 RECK 低表达。外泌体 miR-182 可被细胞吸收和转染。外泌体 miR-182 抑制 RECK 表达并促进 GC 细胞的迁移和侵袭。
外泌体 miR-182 可通过抑制 RECK 显著促进 GC 细胞的迁移和侵袭;因此,miR-182 可作为 GC 的治疗靶点。