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长链非编码 RNA ZNFX1-AS1 通过靶向 miR-193a-3p/SDC1 调节膀胱癌细胞的增殖、迁移和侵袭。

LncRNA ZNFX1-AS1 targeting miR-193a-3p/SDC1 regulates cell proliferation, migration and invasion of bladder cancer cells.

机构信息

Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, P.R. China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 May;24(9):4719-4728. doi: 10.26355/eurrev_202005_21160.

Abstract

OBJECTIVE

Long non-coding RNA (lncRNA) is closely associated with cancer occurrence and tumor development. However, the biological function of lncRNA ZNFX1-AS1 has not yet been reported in bladder cancer. The present study aimed to study the function of ZNFX1-AS1 in bladder cancer cells and the mechanism involved.

PATIENTS AND METHODS

The expression of ZNFX1-AS1 in bladder cancer tumor tissues and cell lines was examined by qRT-PCR. The effects of ZNFX1-AS1 knockdown on cell proliferation, cell cycle, cell migration, and invasion were assessed by Cell Counting Kit-8, flow cytometry (FCM), and transwell assays. Bioinformatics analyses and Luciferase reporter assays were performed to explore the mechanism by which ZNFX1-AS1 exerted its oncogenesis role in bladder cancer. The anti-tumor effect of ZNFX1-AS1 silencing on bladder cancer in vivo was also evaluated.

RESULTS

ZNFX1-AS1 was over-expressed in bladder cancer tumor tissues and cell lines. ZNFX1-AS1 expression was found to be associated with tumor size and advanced clinical stage in patients with bladder cancer. Downregulation of ZNFX1-AS1 inhibited cell proliferation, cell clone formation, migration, and invasion of bladder cancer cells. ZNFX1-AS1 was found to interact with miR-193a-3p/Syndecan 1 (SDC1). ZNFX1-AS1 expression was negatively correlated with miR-193a-3p expression, but positively correlated with SDC1 expression in bladder cancer samples. ZNFX1-AS1 knockdown also effectively suppressed tumor growth in an in vivo xenograft model.

CONCLUSIONS

ZNFX1-AS1 regulated bladder cancer progression by targeting the miR-193a-3p/SDC1 axis. Our study may provide novel insights for bladder cancer prognosis and therapy.

摘要

目的

长链非编码 RNA(lncRNA)与癌症的发生和肿瘤的发展密切相关。然而,lncRNA ZNFX1-AS1 在膀胱癌中的生物学功能尚未报道。本研究旨在研究 ZNFX1-AS1 在膀胱癌细胞中的功能及其涉及的机制。

患者和方法

通过 qRT-PCR 检测膀胱癌肿瘤组织和细胞系中 ZNFX1-AS1 的表达。通过细胞计数试剂盒-8(Cell Counting Kit-8)、流式细胞术(Flow cytometry,FCM)和 Transwell 测定评估 ZNFX1-AS1 敲低对细胞增殖、细胞周期、细胞迁移和侵袭的影响。通过生物信息学分析和荧光素酶报告基因实验探讨 ZNFX1-AS1 在膀胱癌中发挥致癌作用的机制。还评估了 ZNFX1-AS1 沉默对膀胱癌体内抗肿瘤作用。

结果

ZNFX1-AS1 在膀胱癌肿瘤组织和细胞系中过表达。在膀胱癌患者中,ZNFX1-AS1 的表达与肿瘤大小和临床晚期有关。下调 ZNFX1-AS1 抑制膀胱癌细胞的增殖、细胞克隆形成、迁移和侵袭。发现 ZNFX1-AS1 与 miR-193a-3p/ Syndecan 1(SDC1)相互作用。ZNFX1-AS1 的表达与膀胱癌样本中 miR-193a-3p 的表达呈负相关,与 SDC1 的表达呈正相关。在体内异种移植模型中,ZNFX1-AS1 敲低也能有效抑制肿瘤生长。

结论

ZNFX1-AS1 通过靶向 miR-193a-3p/SDC1 轴调控膀胱癌的进展。我们的研究可能为膀胱癌的预后和治疗提供新的思路。

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