环状 RNA 002059 通过 miR-182/MTSS1 轴抑制胃癌细胞增殖和迁移。

Circ_002059 suppresses cell proliferation and migration of gastric cancer via miR-182/MTSS1 axis.

机构信息

Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2021 Mar 26;53(4):454-462. doi: 10.1093/abbs/gmab015.

Abstract

Circular RNAs (circRNAs) play either oncogenic or tumor suppressive roles in gastric cancer (GC). A previous study demonstrated that circ_002059, a typical circRNA, was downregulated in GC tissues. However, the role and mechanism of circ_002059 in GC development are still unknown. In this study, the levels of circ_002059, miR-182, and metastasis suppressor-1 (MTSS1) were examined by real-time quantitative polymerase chain reaction and western blot analysis. Cell proliferation and migration were evaluated by MTT assay and Transwell migration assay, respectively. The interactions between miR-182 and circ_002059 or MTSS1 were analyzed by dual-luciferase reporter assay. A GC xenograft model was established to validate the role of circ_002059 in GC progression in vivo. Overexpression of circ_002059 significantly inhibited, whereas knockdown of circ_002059 notably facilitated, cell proliferation and migration in GC cells. MTSS1 was found to be a direct target of miR-182 and circ_002059 upregulated MTSS1 expression by competitively sponging miR-182. Transfection with miR-182 mimic and MTSS1 silencing abated the inhibitory effect of circ_002059 on GC progression. Circ_002059 inhibited GC cell xenograft tumor growth by regulating miR-182 and MTSS1 expression. Collectively, Circ_002059 inhibited GC cell proliferation and migration in vitro and xenograft tumor growth in mice, by regulating the miR-182/MTSS1 axis.

摘要

环状 RNA（circRNAs）在胃癌（GC）中发挥致癌或抑癌作用。先前的研究表明，circ_002059 是一种典型的 circRNA，在 GC 组织中表达下调。然而，circ_002059 在 GC 发展中的作用和机制尚不清楚。在本研究中，通过实时定量聚合酶链反应和 Western blot 分析检测 circ_002059、miR-182 和转移抑制因子 1（MTSS1）的水平。通过 MTT 测定和 Transwell 迁移测定分别评估细胞增殖和迁移。通过双荧光素酶报告基因测定分析 miR-182 与 circ_002059 或 MTSS1 的相互作用。建立 GC 异种移植模型以验证 circ_002059 在体内 GC 进展中的作用。circ_002059 的过表达显著抑制，而 circ_002059 的敲低则显著促进 GC 细胞的增殖和迁移。发现 MTSS1 是 miR-182 的直接靶标，circ_002059 通过竞争性地吸附 miR-182 而上调 MTSS1 表达。转染 miR-182 模拟物和 MTSS1 沉默减弱了 circ_002059 对 GC 进展的抑制作用。circ_002059 通过调节 miR-182 和 MTSS1 表达抑制 GC 细胞异种移植肿瘤生长。总之，circ_002059 通过调节 miR-182/MTSS1 轴抑制 GC 细胞体外增殖和迁移以及异种移植肿瘤生长。