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微小 RNA-99b 通过抑制 PI3K/AKT/mTOR 信号通路抑制人宫颈癌细胞活性。

MicroRNA-99b suppresses human cervical cancer cell activity by inhibiting the PI3K/AKT/mTOR signaling pathway.

机构信息

Department of Obstetrics and Gynecology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

J Cell Physiol. 2019 Jun;234(6):9577-9591. doi: 10.1002/jcp.27645. Epub 2018 Nov 27.

Abstract

Cervical cancer is common cancer among women with high morbidity. MicroRNAs (miRs) are involved in the progression and development of cervical cancer. This study aimed to explore the effect of miR-99b-5p (miR-99b) on invasion and migration in cervical cancer through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway. The microarray-based analysis was used to screen out differentially expressed miRNAs. Expression of miR-99b, PI3K, AKT, mTOR, and ribosomal protein S6 kinase (p70S6K) was determined in both cervical cancer tissues and paracancerous tissues. Next, alteration of miR-99b expression in cervical cancer was conducted to evaluate levels of PI3K, AKT, mTOR, p70S6K matrix metallopeptidase 2, epithelial cell adhesion molecule, and intercellular adhesion molecule 1, as well as the effect of miR-99b on cell proliferation, invasion, migration, cell cycle distribution, and apoptosis. The results demonstrated that miR-99b expression was decreased and levels of PI3K, AKT, mTOR, and p70S6K were elevated in cervical cancer tissues. More important, overexpressed miR-99b repressed the PI3K/AKT/mTOR signaling pathway, inhibited cell proliferation, invasion, and migration, blocked cell cycle entry, and promoted apoptosis in cervical cancer. These results indicate that miR-99b attenuates the migration and invasion of human cervical cancer cells through downregulation of the PI3K/AKT/mTOR signaling pathway, which provides a therapeutic approach for cervical cancer treatment.

摘要

宫颈癌是一种发病率较高的女性常见癌症。微小 RNA(miRNA)参与宫颈癌的发生和发展。本研究旨在通过磷脂酰肌醇 3-激酶(PI3K)/蛋白激酶 B(AKT)/雷帕霉素靶蛋白(mTOR)信号通路探讨 miR-99b-5p(miR-99b)对宫颈癌侵袭和迁移的影响。采用基于微阵列的分析筛选差异表达的 miRNA。检测宫颈癌组织和癌旁组织中 miR-99b、PI3K、AKT、mTOR 和核糖体蛋白 S6 激酶(p70S6K)的表达。接着,改变宫颈癌中 miR-99b 的表达水平,评估 PI3K、AKT、mTOR、p70S6K 基质金属蛋白酶 2、上皮细胞黏附分子和细胞间黏附分子 1 的水平,以及 miR-99b 对细胞增殖、侵袭、迁移、细胞周期分布和凋亡的影响。结果表明,miR-99b 在宫颈癌组织中表达降低,PI3K、AKT、mTOR 和 p70S6K 水平升高。更为重要的是,过表达 miR-99b 抑制了 PI3K/AKT/mTOR 信号通路,抑制了宫颈癌细胞的增殖、侵袭和迁移,阻止了细胞周期进入,并促进了凋亡。这些结果表明,miR-99b 通过下调 PI3K/AKT/mTOR 信号通路,减轻了人宫颈癌的迁移和侵袭,为宫颈癌的治疗提供了一种方法。

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