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环状 RNA Circ_0000118 通过调控 miR-211-5p/miR-377-3p/AKT2 轴调节宫颈癌癌细胞的恶性程度。

CircRNA Circ_0000118 Regulates Malignancy of Cervical Cancer Cells by Regulating miR-211-5p/miR-377-3p/AKT2 Axis.

机构信息

Department of Obstetrics and Gynecology, Chunan County Traditional Chinese Medicine Hospital, No.1 Xin'an West Road, Chun'an, Hangzhou, 311700, Zhejiang, China.

出版信息

Biochem Genet. 2023 Aug;61(4):1625-1644. doi: 10.1007/s10528-023-10332-w. Epub 2023 Jan 31.

Abstract

CircRNAs are implicated in the development of several cancers. Nevertheless, the involvement of circ_0000118 in the development of cervical cancer (CC) remains unclear. Circ_0000118 levels in tumor tissues and cells were examined by qRT-PCR. The function of circ_0000118 in regulating the malignancy of CC cells was investigated using functional assays, including CCK-8, colony formation, transwell, and tube formation experiments. The functional interaction between circ_0000118 and microRNAs were validated by dual-luciferase activity assay and RNA precipitation experiments. In vivo mouse model was employed to assess the effect of circ_0000118 in the tumorigenesis of CC cells. Circ_0000118 was overexpressed in CC cells and tissues. Loss-of-function experiments demonstrated that circ_0000118 knockdown impaired the proliferation and tumor sphere formation, as well as the angiogenic potential of CC cells. RNA interaction experiments confirmed that circ_0000118 sponged miR-211-5p and miR-377-3p. AKT2 was found to be a target gene negatively modulated by miR-211-5p and miR-377-3p. AKT2 overexpression rescued the inhibition of circ_0000118 downregulation on CC cells. Our study suggested that circ_0000118 functions as an oncogenic factor in progression of CC by maintaining AKT2 level through targeting miR-211-5p and miR-377-3p as a ceRNA (competitive endogenous RNA), which provides novel therapeutic target in the management of CC.

摘要

CircRNAs 参与了几种癌症的发展。然而,circ_0000118 在宫颈癌 (CC) 发展中的作用仍不清楚。通过 qRT-PCR 检测肿瘤组织和细胞中的 circ_0000118 水平。通过 CCK-8、集落形成、transwell 和管形成实验等功能测定研究 circ_0000118 调节 CC 细胞恶性的功能。通过双荧光素酶活性测定和 RNA 沉淀实验验证 circ_0000118 与 microRNAs 之间的功能相互作用。采用体内小鼠模型评估 circ_0000118 对 CC 细胞肿瘤发生的影响。Circ_0000118 在 CC 细胞和组织中过表达。功能丧失实验表明,circ_0000118 敲低可损害 CC 细胞的增殖和肿瘤球形成以及血管生成潜力。RNA 相互作用实验证实 circ_0000118 可吸附 miR-211-5p 和 miR-377-3p。发现 AKT2 是受 miR-211-5p 和 miR-377-3p 负调控的靶基因。AKT2 过表达可挽救 circ_0000118 下调对 CC 细胞的抑制作用。我们的研究表明,circ_0000118 通过作为 ceRNA(竞争内源 RNA)靶向 miR-211-5p 和 miR-377-3p 来维持 AKT2 水平,从而在 CC 进展中发挥致癌因子的作用,为 CC 的治疗提供了新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/665e/10371915/510e5e697659/10528_2023_10332_Fig1_HTML.jpg

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