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miR-1247通过其下游靶点RAB36对膀胱癌细胞增殖和侵袭的抑制作用。

Inhibition of miR-1247 on cell proliferation and invasion in bladder cancer through its downstream target of RAB36.

作者信息

Zhu Yudi, Liang Shaosi, Pan Huafeng, Cheng Zhongliang, Rui Xin

机构信息

Department of Urology, Ningbo No. 2 Hospital, Ningbo, Zhejiang, China,

出版信息

J Biosci. 2018 Jun;43(2):365-373.

Abstract

Recently, microRNA-1247 (miR-1247) has been reported to function as tumour suppressor in several cancer types, including pancreatic cancer, hepatocellular cancer and lung cancer. However, the biological function of miR-1247 in bladder cancer and the underlying mechanisms have remained largely uncovered. In this study, the expression of miR-1247 was significantly downregulated, while RAB36 protein was remarkably upregulated in bladder cancer tissues and cell lines compared with that in paired adjacent normal tissues or normal cell line (SU-HUC-1). The function of miR-1247 and RAB36 in the cell viability, proliferation and invasion of bladder cancer cells (T24 and J82) was assessed by CCK-8, colony formation and Transwell assay, respectively. Gain of function studies showed that upregulation of miR-1247 significantly inhibited cell proliferation and invasion capacity of bladder cancer cells. Consistently, downregulation of RAB36 mimicked the suppressive effects of miR-1247 overexpression in bladder cancer cells. Importantly, miR-1247 was confirmed to target the 30untranslated region (UTR) of RAB36 and downregulated its expression using luciferase reporter assay and Western blot assays. In conclusion, these results provide the first clues regarding the role of miR-1247 might be a potential therapeutic agent and diagnostic marker of bladder cancer by inhibiting RAB36 expression.

摘要

最近,有报道称微小RNA-1247(miR-1247)在包括胰腺癌、肝细胞癌和肺癌在内的几种癌症类型中发挥肿瘤抑制作用。然而,miR-1247在膀胱癌中的生物学功能及其潜在机制在很大程度上仍未被揭示。在本研究中,与配对的相邻正常组织或正常细胞系(SU-HUC-1)相比,miR-1247在膀胱癌组织和细胞系中的表达显著下调,而RAB36蛋白则显著上调。分别通过CCK-8、集落形成和Transwell实验评估了miR-1247和RAB36对膀胱癌细胞(T24和J82)的细胞活力、增殖和侵袭的作用。功能获得性研究表明,miR-1247的上调显著抑制了膀胱癌细胞的增殖和侵袭能力。同样,RAB36的下调模拟了miR-1247过表达对膀胱癌细胞的抑制作用。重要的是,通过荧光素酶报告基因实验和蛋白质免疫印迹实验证实miR-1247靶向RAB36的3'非翻译区(UTR)并下调其表达。总之,这些结果首次揭示了miR-1247的作用,它可能通过抑制RAB36的表达成为膀胱癌的潜在治疗药物和诊断标志物。

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