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miR-186-3p 通过靶向胰岛素样生长因子 1 抑制 PI3K-Akt 信号通路来抑制宫颈癌的发生。

miR-186-3p attenuates the tumorigenesis of cervical cancer via targeting insulin-like growth factor 1 to suppress PI3K-Akt signaling pathway.

机构信息

Department of Radiotherapy, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei, China.

出版信息

Bioengineered. 2021 Dec;12(1):7079-7092. doi: 10.1080/21655979.2021.1977053.

Abstract

miR-186-3p acts as a tumor suppressor in various cancers. This study aimed to explore the expression levels of miR-186-3p and its role in cervical cancer. We analyzed the effects of miR-186-3p and insulin-like growth factor 1 (IGF1) on the proliferation, invasion, and apoptosis of cervical cancer cells in vitro by regulating the PI3K/Akt signaling pathway. In cervical cancer tissues and cells, miR-186-3p was downregulated, and IGF1 was upregulated. In addition, miR-186-3p inhibited cell proliferation and invasion and enhanced apoptosis of cervical cancer cells. Moreover, our results showed that miR-186-3p inversely regulated the mRNA expression of IGF1 through direct contact. Knockdown of IGF1 reversed the results of miR-186-3p inhibitor in cervical cancer cells. In addition, the PI3K/Akt signaling pathway was activated by the miR-186-3p inhibitor, although partially arrested by IGF1 knockdown. The PI3K/Akt signaling pathway inhibitor suppressed miR-186-3p inhibitor-stimulated cell proliferation in cervical cancer. In conclusion, miR-186-3p inhibits tumorigenesis of cervical cancer by repressing IGF1, which inactivates the PI3K/Akt signaling pathway, implicating miR-186-3p as a potential new target for the treatment of cervical cancer.

摘要

miR-186-3p 在多种癌症中充当肿瘤抑制因子。本研究旨在探讨 miR-186-3p 的表达水平及其在宫颈癌中的作用。我们通过调节 PI3K/Akt 信号通路,分析了 miR-186-3p 和胰岛素样生长因子 1(IGF1)对体外宫颈癌细胞增殖、侵袭和凋亡的影响。在宫颈癌组织和细胞中,miR-186-3p 下调,IGF1 上调。此外,miR-186-3p 抑制宫颈癌细胞的增殖和侵袭,增强细胞凋亡。而且,我们的结果表明,miR-186-3p 通过直接接触反向调节 IGF1 的 mRNA 表达。IGF1 的敲低逆转了 miR-186-3p 抑制剂在宫颈癌细胞中的作用。此外,PI3K/Akt 信号通路被 miR-186-3p 抑制剂激活,尽管部分被 IGF1 敲低阻滞。PI3K/Akt 信号通路抑制剂抑制了 miR-186-3p 抑制剂刺激的宫颈癌细胞增殖。总之,miR-186-3p 通过抑制 IGF1 抑制宫颈癌的肿瘤发生,从而使 PI3K/Akt 信号通路失活,表明 miR-186-3p 可能成为治疗宫颈癌的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/864e/8806770/77d8e7426204/KBIE_A_1977053_F0001_OC.jpg

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