Zhou Yan, An Qi, Guo Rui-Xia, Qiao Yu-Huan, Li Liu-Xia, Zhang Xiao-Yan, Zhao Xian-Lan
Department of Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China.
Department of Clinical Pharmacology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China.
Life Sci. 2017 Feb 15;171:9-15. doi: 10.1016/j.lfs.2017.01.006. Epub 2017 Jan 9.
Aberrant expression of miRNAs exert the critical roles in carcinogenesis, including cervical cancer. Recent study corroborated the down-regulation of miR424-5p in uterine cervix adenocarcinoma. This research aimed to investigate the function and underlying mechanisms of miR424-5p in cervical cancer cell growth.
Tissues samples were collected from patients with cervical cancer and healthy control. The expression levels of miR424-5p were determined by qRT-PCR. After transfection with miR424-5p mimics or inhibitor, cervical cancer cell proliferation and apoptosis were evaluated by WST-1 and flow cytometry assay, respectively. The underlying mechanism involved in aforementioned processes was also explored.
Expression of miR424-5p was notably decreased in cervical cancer tissues and cells. Overexpression of miR424-5p restrained cell proliferation and promoted cell apoptosis, but with little function in miR424-5p inhibitor-treated groups. Furthermore, KDM5B was identified as a direct target of miR424-5p as the evidence that miR-424-5p inhibited KDM5B expression and luciferase activity of KDM5B 3'-UTR. Here, KDM5B elevation majorly reversed miR424-5p-triggered inhibition in cell proliferation and increase in cell apoptosis. Moreover, silencing KDM5B expression also restrained cell growth. Additionally, miR424-5p overexpression inhibited the expression of Notch1 and Notch2, which was obviously rescued after KDM5B up-regulation. Simultaneously, blocking KDM5B also attenuated the activation of Notch pathway. Importantly, treatment with Notch agonist Jagged1 antagonized miR424-5p-mediated suppression on cell growth.
This research suggests that miR424-5p may act as a novel anti-oncogene in cervical cancer by blocking cell growth through targeting KDM5B-Notch pathway. Accordingly, our study will support a promising therapeutic strategy against cervical carcinoma.
微小RNA（miRNA）的异常表达在包括宫颈癌在内的肿瘤发生过程中发挥关键作用。最近的研究证实了miR424 - 5p在子宫颈腺癌中表达下调。本研究旨在探讨miR424 - 5p在宫颈癌细胞生长中的功能及潜在机制。
收集宫颈癌患者和健康对照者的组织样本。通过qRT - PCR测定miR424 - 5p的表达水平。用miR424 - 5p模拟物或抑制剂转染后，分别通过WST - 1和流式细胞术检测宫颈癌细胞的增殖和凋亡情况。还探讨了上述过程中涉及的潜在机制。
miR424 - 5p在宫颈癌组织和细胞中的表达显著降低。miR424 - 5p的过表达抑制细胞增殖并促进细胞凋亡，但在miR424 - 5p抑制剂处理组中作用较小。此外，KDM5B被鉴定为miR424 - 5p的直接靶标，证据是miR - 424 - 5p抑制KDM5B的表达以及KDM5B 3'-UTR的荧光素酶活性。在此，KDM5B的升高主要逆转了miR424 - 5p引发的细胞增殖抑制和细胞凋亡增加。此外，沉默KDM5B的表达也抑制细胞生长。另外，miR424 - 5p的过表达抑制了Notch1和Notch2的表达，在KDM5B上调后明显恢复。同时，阻断KDM5B也减弱了Notch信号通路的激活。重要的是，用Notch激动剂Jagged1处理可拮抗miR424 - 5p介导的对细胞生长的抑制作用。
本研究表明，miR424 - 5p可能通过靶向KDM5B - Notch信号通路阻断细胞生长，从而在宫颈癌中作为一种新的抑癌基因发挥作用。因此，我们的研究将支持一种有前景的宫颈癌治疗策略。
