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MicroRNA-520b 通过抑制 Cullin 泛素连接酶结构域缺失蛋白 1（DCUN1D1）在结直肠癌中发挥肿瘤抑制作用。

MicroRNA-520b Functions as a Tumor Suppressor in Colorectal Cancer by Inhibiting Defective in Cullin Neddylation 1 Domain Containing 1 (DCUN1D1).

机构信息

Minimally Invasive Surgery Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China.

Department of Gastrointestinal Surgery, People's Hospital of Linyi City, Linyi, Shandong, P.R. China.

出版信息

Oncol Res. 2018 May 7;26(4):593-604. doi: 10.3727/096504017X14920318811712. Epub 2017 May 4.

DOI:10.3727/096504017X14920318811712
PMID:28470146
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7844770/
Abstract

MicroRNAs (miRs), a class of small noncoding RNAs, are important regulators for gene expression through directly binding to the 3'-untranslated region (3'-UTR) of their target mRNA. Recently, downregulation of miR-520b has been observed in several common human cancers. However, the exact role of miR-520b in colorectal cancer (CRC) has not previously been studied. In this study, our data showed that miR-520b was significantly downregulated in CRC and cell lines when compared with adjacent normal tissues and a normal intestinal epithelial cell line. Low expression of miR-520b was notably associated with the malignant progress and a shorter survival time for CRC patients. Restoration of miR-520b inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in CRC cells. Defective in cullin neddylation 1 domain containing 1 (DCUN1D1) was then identified as a novel target gene of miR-520b in CRC cells. The expression of DCUN1D1 was significantly increased in CRC, with a negative correlation to miR-520b expression in CRC tissues. Moreover, a high expression of DCUN1D1 was significantly associated with the malignant progress and a poor prognosis for CRC patients. Furthermore, overexpression of DCUN1D1 rescued the miR-520b-mediated malignant phenotypes and EMT in CRC cells. The data demonstrate that miR-520b functions as a tumor suppressor in CRC through targeting DCUN1D1, suggesting that miR-520b may become a potential therapeutic target for the treatment of CRC.

摘要

微小 RNA（miRs）是一类小的非编码 RNA，通过直接与靶 mRNA 的 3'非翻译区（3'-UTR）结合，是基因表达的重要调节剂。最近，几种常见的人类癌症中观察到 miR-520b 的下调。然而，miR-520b 在结直肠癌（CRC）中的确切作用尚未得到研究。在这项研究中，与相邻正常组织和正常肠上皮细胞系相比，我们的数据显示 miR-520b 在 CRC 和细胞系中显着下调。miR-520b 的低表达与 CRC 患者的恶性进展和较短的生存时间显着相关。miR-520b 的恢复抑制了 CRC 细胞的增殖、迁移、侵袭和上皮-间充质转化（EMT）。然后鉴定出 DCUN1D1（cullin neddylation 1 结构域包含 1）是 CRC 细胞中 miR-520b 的新型靶基因。CRC 中 DCUN1D1 的表达显着增加，与 CRC 组织中 miR-520b 的表达呈负相关。此外，DCUN1D1 的高表达与 CRC 患者的恶性进展和不良预后显着相关。此外，DCUN1D1 的过表达挽救了 miR-520b 介导的 CRC 细胞中的恶性表型和 EMT。数据表明，miR-520b 通过靶向 DCUN1D1 在 CRC 中发挥肿瘤抑制作用，表明 miR-520b 可能成为 CRC 治疗的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3806/7844770/497d998e4492/OR-26-593-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3806/7844770/497d998e4492/OR-26-593-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3806/7844770/e465136dfdbc/OR-26-593-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3806/7844770/1a0a5984d994/OR-26-593-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3806/7844770/cfddf2b553d3/OR-26-593-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3806/7844770/89cbac0f27bf/OR-26-593-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3806/7844770/ff0a6b5662b6/OR-26-593-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3806/7844770/497d998e4492/OR-26-593-g007.jpg

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