MicroRNA-1298-5p通过下调连接蛋白43抑制膀胱癌细胞增殖和侵袭。

Gang Li, Longfeng Sun, Zhong-yi Mu, Shi-bo Liu, Hong-Chen Qu, Qingpeng Xie, Bin Hu
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引用次数: 16

摘要

MicroRNA (miR)-1298在多种恶性肿瘤中广泛下调,促进细胞增殖、侵袭和迁移。然而,miR-1298在膀胱癌(BC)中的具体生物学功能尚不清楚。连接蛋白43 (Cx43)在不同的肿瘤中经常上调。在BC中鉴定靶向Cx43的mirna将有助于开发基于Cx43的BC治疗方法。本研究结果显示,miR-1298和Cx43在BC临床组织中的表达水平分别显著下调和上调。通过MTT试验、细胞周期试验、集落形成试验、transwell试验、明胶酶谱法和western blot, miR-1298过表达分别抑制了两种BC细胞系的细胞增殖、迁移和侵袭。此外,我们发现miR-1298通过直接靶向3'-UTR降低Cx43的表达。接下来,我们观察到Cx43对BC细胞增殖、迁移和侵袭的促进作用可以被miR-1298过表达部分减弱。此外,转染过表达的mir -1298后,p-ERK的蛋白表达得到改善。Cx43的敲低逆转了miR-1298表达降低对细胞迁移和侵袭的促进作用。所有数据表明,miR-1298可能是一种潜在的治疗剂和通过抑制Cx43来诊断BC的标志物。
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MicroRNA-1298-5p inhibits cell proliferation and invasion of bladder cancer via downregulating connexin 43.
MicroRNA (miR)-1298 is widely down-regulated in various malignant tumors, which facilitates cell proliferation, invasion and migration. However, the specific biological function of miR-1298 in bladder cancer (BC) is still unknown. Connexin 43 (Cx43) is often up-regulated in different tumors. Identifying miRNAs that target Cx43 in the setting of BC will help to develop Cx43-based therapies for BC. In this study, the results demonstrated that the expression levels of miR-1298 and Cx43 were significantly down-regulated and up-regulated in BC clinical tissues, respectively. The overexpression of miR-1298 inhibited cell proliferation, migration, and invasion in two BC cell lines via MTT assay, cell cycle assay, colony formation assay, transwell assay, gelatin zymography, and western blot, respectively. In addition, it was found that miR-1298 decreased Cx43 expression by directly targeting the 3'-UTR. Following, we observed that the promotion effect of Cx43 on BC cell proliferation, migration, and invasion could be partially attenuated by miR-1298 overexpression. Moreover, the protein expression of p-ERK was ameliorated after transfected with overexpressed-miR-1298. The knockdown of Cx43 reversed the promotion effect of cell migration and invasion due to the decreased miR-1298 expression. All data suggest miR-1298 might be a potential therapeutic agent and diagnostic marker of BC by inhibiting Cx43.
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