切换至 "中华医学电子期刊资源库"
高级检索
中华腔镜泌尿外科杂志(电子版)

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

所属专题： 文献；

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. 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. 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:
全文 ( ) 下载PDF ( ) 导出引用
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]. 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]. 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
[1]
Bostwick DG, Burke HB, Djakiew D, et al. Humanprostate cancer risk factors[J]. Cancer, 2004, 101 (10 Suppl): 2371-490.
[2]
Fang YX, Gao WQ. Roles of microRNAs during prostatic tumorigenesis and tumor progression[J]. Oncogene, 2014，33(2): 135-147.
[3]
Kim WT, Kim WJ. MicroRNAs in prostate cancer[J]. Prostate Int, 2013, 1(1): 3-9.
[4]
Ling XH, Fu H, Chen ZY, et al. miR 505 suppresses prostate cancer progression by targeting NRCAM[J]. Oncol Rep, 2019, 42(3): 991-1004.
[5]
Qin Z, He W, Tang J, et al. MicroRNAs provide feedback regulation of epithelial-mesenchymal transition induced by growth factors[J]. J Cell Physiol. 2016, 231(1): 120-129.
[6]
Yamamoto Y, Yoshioka Y, Minoura K, et al. An integrative genomic analysis revealed the relevance of microRNA and gene expression for drugresistance in human breast cancer cells[J]. Mol Cancer, 2011, 10(1): 135.
[7]
Chen S, Sun KX, Liu BL, et al.MicroRNA-505 functions as a tumor suppressor in endometrial cancer by targeting TGF-α[J]. Mol Cancer, 2016, 15(1): 11.
[8]
Lu L, Qiu C, Li D, et al. MicroRNA-505 suppresses proliferation and invasion in hepatoma cells by directly targeting high-mobility group box 1[J]. Life Sci, 2016, 157: 12-18.
[9]
Harley RJ, Murdy JP, Wang Z, et al. Neuronal cell adhesion molecule (NrCAM) is expressed by sensory cells in the cochlea and is necessary for proper cochlear innervation and sensory domain patterning during development[J]. Dev Dyn, 2018, 247(7): 934-950.
[10]
Lokapally A, Metikala S, Hollemann T. Xenopus laevis neuronal cell adhesion molecule (nrcam): plasticity of a CAM in the developing nervous system[J]. Dev Genes Evol. 2017, 227(1): 61-67.
[11]
Fitzli D, Stoeckli ET, Kunz S, et al. A direct interaction of axonin-1 with NgCAM-related cell adhesion molecule (NrCAM) results in guidance, but not growth of commissural axons[J]. J Cell Biol, 2000, 149(4): 951-968.
[12]
Chan JY, Ong CW, Salto-Tellez M.Overexpression of neurone glial-related cell adhesion molecule is an independent predictor of poor prognosis in advanced colorectal cancer[J].Cancer Sci, 2011, 102(10): 1855-1861.
[13]
Conacci-Sorrell M, Kaplan A, Raveh S, et al.The shed ectodomain of Nr-CAM stimulates cell proliferation and motility, and confers cell transformation[J].Cancer Res, 2005, 65(24): 11605-11612.
[14]
Zhang Y, Sui F, Ma J, et al. Positive feedback loops between nrcam and major signaling pathways contribute to thyroid tumorigenesis[J]. J Clin Endocrinol Metab, 2017, 102(2): 613-624.
[15]
Górka B, Skubis-Zegadło J, Mikula M,et al. NrCAM, a neuronal system cell-adhesion molecule, is induced in papillary thyroid carcinomas[J]. Br J Cancer. 200, 97(4): 531-538.
[1] 方晔, 谢晓红, 罗辉. 品管圈在提高前列腺癌穿刺检出率中的应用[J]. 中华医学超声杂志（电子版）, 2023, 20(07): 722-727.
[2] 傅子财, 戴冠东, 朱伟民, 陆伟, 熊建义, 王大平, 邓桢翰. 过氧化物酶体增殖物激活受体在骨关节炎中的研究进展[J]. 中华关节外科杂志(电子版), 2023, 17(03): 363-367.
[3] 江振剑, 蒋明, 黄大莉. TK1、Ki67蛋白在分化型甲状腺癌组织中的表达及预后价值研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 623-626.
[4] 李全喜, 唐辉军, 张健生, 杨飞. 基于MUSE-DWI与SS-DWI技术在前列腺癌图像中的对比研究[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(06): 553-557.
[5] 梅津熠, 王燕, 瞿旻, 董振阳, 周增辉, 沈显琦, 李嘉伦, 高旭. 机器人前列腺癌根治术中"膀胱外中叶"的处理[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(05): 429-433.
[6] 穆靖军, 马增妮, 曹晓明. 临床局限性前列腺癌包膜外侵犯的危险因素分析[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(04): 326-331.
[7] 李全喜, 唐辉军, 唐友杰, 杨飞. DISCO成像技术在前列腺增生与前列腺癌鉴别诊断中的应用价值[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(04): 332-335.
[8] 王邦郁, 陈晓鹏, 唐国军, 王佳妮. 尿液细胞外囊泡circRNA分类器对高级别前列腺癌诊断价值的初步研究[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(04): 339-342.
[9] 刘硕儒, 王功炜, 张斌, 李书豪, 胡成. 新型溶瘤病毒M1激活内质网应激致前列腺癌细胞凋亡的机制[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(04): 388-393.
[10] 郑嘉裕, 吴建杰, 李小娟, 曾恒达, 李国邦, 黄炯煅, 温星桥. hsa_circ_0090923在前列腺癌中的表达及其对前列腺癌细胞增殖和迁移的调控[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(03): 276-283.
[11] 余慧, 王静, 杜丹, 杨帆. 下调miR-301a-3p抑制人卵巢颗粒KGN细胞增殖和诱导凋亡的机制研究[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(03): 137-143.
[12] 樱峰, 王静, 刘雪清, 李潇. 水通道蛋白1对人角膜内皮细胞增殖、迁移及凋亡影响的实验研究[J]. 中华眼科医学杂志(电子版), 2023, 13(03): 146-151.
[13] 邓世栋, 刘凌志, 郭大勇, 王超, 黄忠欣, 张晖辉. 沉默SNHG1基因对膀胱癌细胞增殖、凋亡、迁移和铁死亡的影响[J]. 中华临床医师杂志(电子版), 2023, 17(07): 804-811.
[14] 王苏贵, 皇立媛, 姜福金, 吴自余, 张先云, 李强, 严大理. 异质性细胞核核糖蛋白A2B1在前列腺癌中的作用及其靶向中药活性成分筛选研究[J]. 中华临床医师杂志(电子版), 2023, 17(06): 731-736.
[15] 方辉, 李菲, 张帆, 魏强, 陈强谱. 外源性瘦素对梗阻性黄疸大鼠肠黏膜增殖的影响[J]. 中华临床医师杂志(电子版), 2023, 17(05): 575-580.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号