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敲低长链非编码 RNA ZNRD1-AS1 通过调控 miR-194 和 ZEB1 抑制膀胱癌的进展。

Knockdown of lncRNA ZNRD1-AS1 inhibits progression of bladder cancer by regulating miR-194 and ZEB1.

机构信息

Department of Imaging And Magnetic Response, the Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, China.

出版信息

Cancer Med. 2020 Oct;9(20):7695-7705. doi: 10.1002/cam4.3373. Epub 2020 Aug 30.

DOI:10.1002/cam4.3373
PMID:32862492
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7571837/
Abstract

BACKGROUND

Bladder cancer (BC) is a common urinary neoplasm with high incidence worldwide. Long noncoding RNA zinc ribbon domain containing 1 antisense RNA 1 (ZNRD1-AS1) has been reported to be upregulated in BC. However, the exact role of ZNRD1-AS1 as well as its mechanism remains poorly understood.

METHODS

Zinc ribbon domain containing 1 antisense RNA 1, and its potential downstream genes microRNA-194 (miR-194) and zinc finger E-box binding homeobox 1 (ZEB1) levels were detected via quantitative real-time polymerase chain reaction or western blot. Cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) were detected to assess the influences of ZNRD1-AS1, miR-194 and ZEB1 on BC cells by colony formation, cell counting kit-8 (CCK-8), transwell analysis or western blot. The relationship between miR-194 and ZNRD1-AS1 or ZEB1 was analyzed by luciferase activity analysis. The xenograft experiment was performed to assess the function of ZNRD1-AS1 in vivo.

RESULTS

Zinc ribbon domain containing 1 antisense RNA 1level was upregulated in BC. ZNRD1-AS1 silence repressed proliferation, migration, invasion and EMT in BC cells. MiR-194 was identified as a target of ZNRD1-AS1, and miR-194 upregulation repressed proliferation, migration, invasion, and EMT by ZNRD1-AS1 sponging. ZEB1 was targeted via miR-194 and its interference impeded proliferation, migration, invasion, and EMT. Moreover, ZNRD1-AS1 regulated ZEB1 expression via miR-194. Besides, inhibition of ZNRD1-AS1 attenuated tumor growth by miR-194/ZEB1 axis in vivo.

CONCLUSION

Knockdown of ZNRD1-AS1 suppressed BC cell development in vitro and in vivo via targeting miR-194 to regulate ZEB1, indicating a novel avenue for treatment of BC.

摘要

背景

膀胱癌（BC）是一种常见的泌尿系统肿瘤，全球发病率较高。长链非编码 RNA 锌指结构域包含 1 反义 RNA 1（ZNRD1-AS1）已被报道在 BC 中上调。然而，ZNRD1-AS1 的确切作用及其机制仍知之甚少。

方法

通过实时定量聚合酶链反应或 Western blot 检测 ZNRD1-AS1 及其潜在下游基因 microRNA-194（miR-194）和锌指 E 盒结合同源盒 1（ZEB1）的水平。通过集落形成、细胞计数试剂盒-8（CCK-8）、Transwell 分析或 Western blot 检测 ZNRD1-AS1、miR-194 和 ZEB1 对 BC 细胞增殖、迁移、侵袭和上皮-间充质转化（EMT）的影响。通过荧光素酶活性分析分析 miR-194 与 ZNRD1-AS1 或 ZEB1 的关系。通过异种移植实验评估 ZNRD1-AS1 在体内的功能。

结果

BC 中 ZNRD1-AS1 水平上调。ZNRD1-AS1 沉默抑制 BC 细胞增殖、迁移、侵袭和 EMT。miR-194 被鉴定为 ZNRD1-AS1 的靶标，miR-194 通过 ZNRD1-AS1 海绵作用抑制增殖、迁移、侵袭和 EMT。ZEB1 是通过 miR-194 靶向的，其干扰阻碍了增殖、迁移、侵袭和 EMT。此外，ZNRD1-AS1 通过 miR-194 调节 ZEB1 的表达。此外，体内抑制 ZNRD1-AS1 通过 miR-194/ZEB1 轴抑制肿瘤生长。

结论

体外和体内抑制 ZNRD1-AS1 通过靶向 miR-194 调节 ZEB1 抑制 BC 细胞的发展，为 BC 的治疗提供了新的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2f8/7571837/2ccac45f7029/CAM4-9-7695-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2f8/7571837/681298fd17f8/CAM4-9-7695-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2f8/7571837/46184c4091fd/CAM4-9-7695-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2f8/7571837/26ce406e1b5d/CAM4-9-7695-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2f8/7571837/64a46a15081b/CAM4-9-7695-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2f8/7571837/1cec6f7e3804/CAM4-9-7695-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2f8/7571837/98edce87f9ec/CAM4-9-7695-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2f8/7571837/2ccac45f7029/CAM4-9-7695-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2f8/7571837/681298fd17f8/CAM4-9-7695-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2f8/7571837/46184c4091fd/CAM4-9-7695-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2f8/7571837/26ce406e1b5d/CAM4-9-7695-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2f8/7571837/64a46a15081b/CAM4-9-7695-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2f8/7571837/1cec6f7e3804/CAM4-9-7695-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2f8/7571837/98edce87f9ec/CAM4-9-7695-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2f8/7571837/2ccac45f7029/CAM4-9-7695-g007.jpg

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