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环状 RNA circ_0000228 通过 microRNA-195-5p/赖氨酰氧化酶样蛋白 2 轴促进宫颈癌的恶性转化。

Circular RNA circ_0000228 promotes the malignancy of cervical cancer via microRNA-195-5p/ lysyl oxidase-like protein 2 axis.

机构信息

Department of Obstetrics and Gynecology, The Third People's Hospital of Linyi, Linyi, Shandong, China.

出版信息

Bioengineered. 2021 Dec;12(1):4397-4406. doi: 10.1080/21655979.2021.1954846.

Abstract

Circular RNAs (circRNAs) are a class of novel non-coding RNAs that are vital in modulating gene expression and biological processes. Nevertheless, in cervical cancer (CC), the role of circRNA is much less investigated. In this work, circ_0000228 expression in CC is measured and circ_0000228's function and related mechanism are investigated. Quantitative real-time quantitative polymerase chain reaction (qRT-PCR) was utilized to examine the expression levels of circ_0000228, microRNA-195-5p (miR-195-5p) and lysyl oxidase-like protein 2 (LOXL2). Western blotting was employed to examine LOXL2 protein expression in CC cell lines. CC cell lines with circ_0000228 knockdown were constructed, and the CCK-8 experiment and Transwell experiment were executed to investigate the effect of circ_0000228 on the malignant characteristics of CC cells. Furthermore, a dual-luciferase reporter gene experiment was applied to validate the targeting relationship between circ_0000228 and miR-195-5p, miR-195-5p and LOXL2. In this study, we demonstrated that circ_0000228 showed a remarkable up-modulation in CC tissues and cell lines. Circ_0000228 knockdown repressed the growth and metastatic potential of CC cells. Mechanistically, circ_0000228 facilitated CC progression through sponging miR-195-5p and up-modulating LOXL2 expression. We conclude that circ_0000228 is an oncogenic circRNA, which participates in promoting CC progression via regulating the miR-195-5p/LOXL2 axis.

摘要

环状 RNA(circRNAs)是一类新型的非编码 RNA,在调节基因表达和生物过程中起着至关重要的作用。然而,在宫颈癌(CC)中,circRNA 的作用研究较少。在这项工作中,测量了 CC 中 circ_0000228 的表达,并研究了 circ_0000228 的功能及相关机制。采用实时定量聚合酶链反应(qRT-PCR)检测 circ_0000228、微小 RNA-195-5p(miR-195-5p)和赖氨酰氧化酶样蛋白 2(LOXL2)的表达水平。采用 Western blot 检测 CC 细胞系中 LOXL2 蛋白的表达。构建 circ_0000228 敲低的 CC 细胞系,并进行 CCK-8 实验和 Transwell 实验,以研究 circ_0000228 对 CC 细胞恶性特征的影响。此外,应用双荧光素酶报告基因实验验证 circ_0000228 与 miR-195-5p、miR-195-5p 与 LOXL2 之间的靶向关系。本研究表明,circ_0000228 在 CC 组织和细胞系中呈现显著上调。circ_0000228 敲低抑制了 CC 细胞的生长和转移潜能。机制上,circ_0000228 通过海绵吸附 miR-195-5p 和上调 LOXL2 表达促进 CC 进展。我们得出结论,circ_0000228 是一种致癌性 circRNA,通过调节 miR-195-5p/LOXL2 轴参与促进 CC 进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4703/8806657/e134b2dd42fd/KBIE_A_1954846_UF0001_OC.jpg

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