NRCAM-PI3K-AKT信号通路影响miR-505对前列腺癌细胞的增殖抑制作用

doi:10.3877/cma.j.issn.1674-3253.2020.02.015

中华腔镜泌尿外科杂志(电子版) ›› 2020, Vol. 14 ›› Issue (02) : 145 -148. doi: 10.3877/cma.j.issn.1674-3253.2020.02.015

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实验研究

NRCAM-PI3K-AKT信号通路影响miR-505对前列腺癌细胞的增殖抑制作用

凌晓辉¹, 陈佳鸿², 陈志云¹, 朱善文¹, 杨盛帮³, 江福能³, 钟惟德³^,^†(

)

^1. 516001　广东，惠州市中心人民医院生殖中心
^2. 516001　广东，惠州市中心人民医院泌尿外科
^3. 510180　广州市第一人民医院，华南理工大学附属第二医院泌尿外科，广东省临床分子医学及分子诊断重点实验室

收稿日期:2019-10-17 出版日期:2020-04-01
通信作者: 钟惟德
基金资助:
惠州市科技计划项目(190409094571998); 广州市科技项目(201803040001，201707010291); 广东省自然科学基金项目(2017A030310593)

NRCAM-PI3K-AKT pathway is involved in the miR-505 induced proliferative suppression of prostate cancer cells

Xiaohui Ling¹, Jiahong Chen², Zhiyun Chen¹, Shanwen Zhu¹, Shengbang Yang³, Funeng Jiang³, Weide Zhong³^,^†()

^1. Reproductive Medicine Centre, Huizhou Central People’s Hospital, Guangdong Medical University, Guangdong 516001, China
^2. Department of Urology, Huizhou Central People’s Hospital, Guangdong Medical University, Guangdong 516001, China
^3. Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, the Second Affiliated Hospital of South China University of Technology, Guangzhou 510180, China

Received:2019-10-17 Published:2020-04-01
Corresponding author: Weide Zhong
About author:
Corresponding author:Zhong Weide, Email: zhongwd2009@live.cn

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引用本文：

凌晓辉, 陈佳鸿, 陈志云, 朱善文, 杨盛帮, 江福能, 钟惟德. NRCAM-PI3K-AKT信号通路影响miR-505对前列腺癌细胞的增殖抑制作用[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2020, 14(02): 145-148.

Xiaohui Ling, Jiahong Chen, Zhiyun Chen, Shanwen Zhu, Shengbang Yang, Funeng Jiang, Weide Zhong. NRCAM-PI3K-AKT pathway is involved in the miR-505 induced proliferative suppression of prostate cancer cells[J/OL]. Chinese Journal of Endourology(Electronic Edition), 2020, 14(02): 145-148.

目的

我们研究已经发现微小RNA-505（miR-505）可靶向调控神经细胞黏着分子（NRCAM）抑制前列腺癌的增殖、侵袭及转移。本研究拟进一步探讨miR-505在前列腺癌动物模型的功能，以及miR-505/NRCAM参与的下游调控信号通路。

方法

建立裸鼠皮下形成异体移植瘤模型，分析miR-505对前列腺癌的增殖力影响，免疫组化进一步探讨其参与的可能通路；在NRCAM抑制表达的人前列腺癌细胞株LNCaP和PC3细胞株中，蛋白质印迹法检测PI3K-AKT信号通路的蛋白表达水平；抑制NRCAM表达的PC3及LNCaP，细胞增殖实验证实NRCAM对细胞增殖力的影响。

结果

裸鼠动物模型发现miR-505过表达细胞株形成的皮下移植瘤明显比对照组的生长速度减缓（P<0.05），并且移植瘤的AKT及EGFR蛋白的表达是明显下降的（P<0.05）。前列腺癌细胞株中，抑制NRCAM的表达均可以导致磷酸化位点的AKT、EGFR及FAK的蛋白水平表达均下调。并且抑制NRCAM的表达，前列腺癌细胞PC3及LNCaP的增殖力下降（P<0.05）。

结论

miR-505可能靶向调控NRCAM，影响PI3K/AKT信号通路的表达，而抑制前列腺癌细胞的增殖力。

关键词: 前列腺癌, NRCAM, miR-505, PI3K/AKT, 增殖

Objective

Our previous study showed that miR-505 can suppress the proliferation, invasion and migration of prostate cancer (PCa) cells by targeting NRCAM. This study is aimed to investigate the role of miR-505 in PCa xenograft mouse models and its downstream signaling that miR-505/NRCAM may be mediated.

Methods

The xenograft mouse models of PCa was used to detect effects of miR-505 on the proliferative ability and the possible downstream pathway. After depletion of NRCAM in PC3 and LNCaP cells, CCK8 assays and Western blotting were chosen to identify the cell proliferation and the activities of PI3K/AKT pathways.

Results

Compared to the control group, the tumor volume and growth rate were significantly slower in PCa xenografts with miR-505 overexpression. Immunohistochemical analysis showed that the PCa xenografts overexpressing miR-505 have significantly lower AKT and EGFR protein than the control xenografts. We further showed that the cells with si-NrCAM transfection exhibited lower viability when compared with the control cell.

Conclusion

Our study may unveil the inhibitory effects of miR-505 on PCa proliferation, possibly by targeting NRCAM via PI3K/AKT signaling.

Key words: Prostate cancer, NRCAM, miR-505, PI3K-AKT pathway, Proliferation

图1 miR-505抑制动物模型的瘤体形成及影响AKT通路的表达

图3 NRCAM抑制表达细胞株的增殖力下降

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