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环状 RNA circ_0000467 通过 miR-382-5p/EN2 轴调控结直肠癌的发生发展。

Circular RNA circ_0000467 regulates colorectal cancer development via miR-382-5p/EN2 axis.

机构信息

Department of Gastroenterology, The People's Hospital of China Three Gorges University and The First People's Hospital of Yichang, Yichang, Hubei Province, China.

出版信息

Bioengineered. 2021 Dec;12(1):886-897. doi: 10.1080/21655979.2021.1889130.

DOI:10.1080/21655979.2021.1889130
PMID:33685351
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8806233/
Abstract

Circular RNAs (CircRNAs), belonging to non-coding RNAs, exert a crucial modulatory role in cancer progression. In this study, circRNA microarray analysis was utilized to screen differentially expressed circRNA in colorectal cancer (CRC) and circ_0000467 was identified as one circRNA whose expression was significantly upregulated in CRC. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) indicated that circ_0000467 and engrailed-2 (EN2) expression levels were up-modulated, while the expression level of miR-382-5p was down-modulated in CRC tissues. The depletion of circ_0000467 expression was found to impede the multiplication, migration, invasion, and epithelial-mesenchymal transition (EMT) processes in CRC cells, which were examined by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and Transwell experiments. Dual-luciferase reporter assay was used to verify the targeting relationship between circ_0000467 and miR-382-5p. It was also revealed that circ_0000467 could up-regulate EN2 expression via repressing miR-382-5p in CRC cells. Furthermore, EN2 overexpression counteracted the suppressing effects of circ_0000467 knockdown on the malignant behaviors of CRC cells. To sum up, circ_0000467 facilitates CRC development by modulating the miR-382-5p/EN2 axis, and circ_0000467 is a promising target for CRC therapy.

摘要

环状 RNA(circRNAs)属于非编码 RNA,在癌症进展中发挥着关键的调节作用。在这项研究中,利用环状 RNA 微阵列分析筛选结直肠癌(CRC)中差异表达的环状 RNA,鉴定出circ_0000467 是一种在 CRC 中表达显著上调的环状 RNA。实时定量逆转录-聚合酶链反应(qRT-PCR)显示,circ_0000467 和 engrailed-2(EN2)的表达水平上调,而 miR-382-5p 的表达水平下调在 CRC 组织中。circ_0000467 表达的耗竭被发现会阻碍 CRC 细胞的增殖、迁移、侵袭和上皮-间充质转化(EMT)过程,这通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐(MTT)和 Transwell 实验进行了检查。双荧光素酶报告基因实验用于验证 circ_0000467 和 miR-382-5p 之间的靶向关系。还表明,circ_0000467 可以通过抑制 CRC 细胞中的 miR-382-5p 而上调 EN2 表达。此外,EN2 的过表达抵消了 circ_0000467 敲低对 CRC 细胞恶性行为的抑制作用。总之,circ_0000467 通过调节 miR-382-5p/EN2 轴促进 CRC 的发展,circ_0000467 是 CRC 治疗的有前途的靶点。

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