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微小RNA-125a-5p通过靶向ABL2调节人宫颈癌的增殖和迁移。

MicroRNA-125a-5p modulates human cervical carcinoma proliferation and migration by targeting ABL2.

作者信息

Qin Xian, Wan Yajun, Wang Saiying, Xue Min

机构信息

Department of Obstetrics and Gynecology, Central South University, Changsha, People's Republic of China.

Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, People's Republic of China.

出版信息

Drug Des Devel Ther. 2015 Dec 24;10:71-9. doi: 10.2147/DDDT.S93104. eCollection 2016.

Abstract

BACKGROUND

In this study, we intended to understand the regulatory mechanisms of microRNA-125a-5p (miR-125a-5p) in human cervical carcinoma.

METHODS

The gene expressions of miR-125a-5p in seven cervical carcinoma cell lines and 12 human cervical carcinoma samples were evaluated by quantitative real-time reverse transcription polymerase chain reaction. Ca-Ski and HeLa cells were transduced with lentivirus carrying miR-125a-5p mimics, and the effects of lentivirus-induced miR-125a-5p upregulation on cervical carcinoma proliferation and migration were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and transwell assays, respectively. In additional, HeLa cells were inoculated into null mice to evaluate the effect of miR-125a-5p upregulation on in vivo cervical carcinoma growth. The direct regulation of miR-125a-5p on its target gene, ABL proto-oncogene 2 (ABL2), in cervical carcinoma was evaluated by quantitative real-time reverse transcription polymerase chain reaction, Western blotting and luciferase reporter assays, respectively. ABL2 was then downregulated by small interfering RNA to examine its effect on cervical carcinoma proliferation and migration.

RESULTS

miR-125a-5p was downregulated in both cervical carcinoma cell lines and human cervical carcinomas. In Ca-Ski and HeLa cells, lentivirus-mediated miR-125a-5p upregulation inhibited cancer proliferation and migration in vitro and cervical carcinoma transplantation in vivo. ABL2 was shown to be directly targeted by miR-125a-5p. In cervical carcinoma, ABL2 gene and protein levels were both downregulated by miR-125a-5p. Small interfering RNA-mediated ABL2 downregulation also had tumor-suppressive effects on cervical carcinoma proliferation and migration.

CONCLUSION

The molecular pathway of miR-125a-5p/ABL2 plays an important role in human cervical carcinoma. Targeting miR-125a-5p/ABL2 pathway may provide a new treatment strategy for patients with cervical carcinoma.

摘要

背景

在本研究中,我们旨在了解微小RNA - 125a - 5p(miR - 125a - 5p)在人宫颈癌中的调控机制。

方法

通过定量实时逆转录聚合酶链反应评估7种宫颈癌细胞系和12例人宫颈癌样本中miR - 125a - 5p的基因表达。用携带miR - 125a - 5p模拟物的慢病毒转导Ca - Ski和HeLa细胞,分别通过3 -(4,5 - 二甲基噻唑 - 2 - 基)- 2,5 - 二苯基四氮唑溴盐和Transwell实验检测慢病毒诱导的miR - 125a - 5p上调对宫颈癌增殖和迁移的影响。此外,将HeLa细胞接种到裸鼠体内以评估miR - 125a - 5p上调对体内宫颈癌生长的影响。分别通过定量实时逆转录聚合酶链反应、蛋白质免疫印迹法和荧光素酶报告基因实验评估miR - 125a - 5p对其靶基因ABL原癌基因2(ABL2)在宫颈癌中的直接调控作用。然后用小干扰RNA下调ABL2以检测其对宫颈癌增殖和迁移的影响。

结果

miR - 125a - 5p在宫颈癌细胞系和人宫颈癌中均下调。在Ca - Ski和HeLa细胞中,慢病毒介导的miR - 125a - 5p上调在体外抑制癌细胞增殖和迁移,在体内抑制宫颈癌移植瘤生长。ABL2被证明是miR - 125a - 5p的直接靶标。在宫颈癌中,miR - 125a - 5p下调ABL2基因和蛋白水平。小干扰RNA介导的ABL2下调对宫颈癌增殖和迁移也具有肿瘤抑制作用。

结论

miR - 125a - 5p/ABL2分子通路在人宫颈癌中起重要作用。靶向miR - 125a - 5p/ABL2通路可能为宫颈癌患者提供新的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc1e/4699546/c8e410266121/dddt-10-071Fig1.jpg

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