MicroRNA-98 通过调控 Wnt/β-catenin 通路靶向 HMGA2 抑制视网膜母细胞瘤的发生发展。
MicroRNA-98 targets HMGA2 to inhibit the development of retinoblastoma through mediating Wnt/β-catenin pathway.
机构信息
Department of Ophthalmology, Jining No.1 People's Hospital, Jining, Shandong, China.
Department of Clinical Laboratory, Rizhao Hospital of TCM, Rizhao, Shandong, China.
出版信息
Cancer Biomark. 2019;25(1):79-88. doi: 10.3233/CBM-182315.
BACKGROUND
Recently, the incidence and mortality of retinoblastoma (RB) have gradually increased. Many studies support the pivotal role of microRNAs (miRNAs) in the pathogenesis of RB. Alternation of microRNA-98 (miR-98) expression has been detected in several cancers, excluding RB. This study was designed to assess the regulatory mechanisms of miR-98 in human RB.
METHODS
RT-qPCR and Western blot analysis were used to detect miR-98 and HMGA2 expression. The effects of miR-98 were explored using the CCK-8 and Transwell assays. Dual-luciferase reporter assay was performed to confirm the relationship between miR-98 and HMGA2.
RESULTS
In RB, downregulation of miR-98 was identified. Upregulation of miR-98 inhibited proliferation, invasion and migration of RB cells. Further, HMGA2 was confirmed as a direct target gene of miR-98. And knockdown of HMGA2 suppressed the progression of RB. Moreover, upregulation of HMGA2 reversed the suppressive effects in the development of RB. In addition, miR-98 also showed suppressive effect on EMT and Wnt/β-catenin pathway.
CONCLUSION
MiR-98 targets HMGA2 to act as a tumor suppressor in RB by mediating Wnt/β-catenin pathway.
背景
近年来，视网膜母细胞瘤（RB）的发病率和死亡率逐渐升高。许多研究支持 microRNAs（miRNAs）在 RB 发病机制中的关键作用。miR-98 的表达改变已在几种癌症中被检测到，而 RB 除外。本研究旨在评估 miR-98 在人 RB 中的调控机制。
方法
采用 RT-qPCR 和 Western blot 分析检测 miR-98 和 HMGA2 的表达。使用 CCK-8 和 Transwell 测定法探索 miR-98 的作用。双荧光素酶报告基因测定法证实 miR-98 与 HMGA2 之间的关系。
结果
在 RB 中，鉴定出 miR-98 的下调。miR-98 的上调抑制了 RB 细胞的增殖、侵袭和迁移。进一步证实 HMGA2 是 miR-98 的直接靶基因。HMGA2 的敲低抑制了 RB 的进展。此外，HMGA2 的上调逆转了 RB 发育过程中的抑制作用。此外，miR-98 还对 EMT 和 Wnt/β-catenin 通路表现出抑制作用。
结论
miR-98 通过介导 Wnt/β-catenin 通路靶向 HMGA2 发挥抑癌作用在 RB 中。
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