miR-485-5p靶向氧连接的N-乙酰氨基葡萄糖转移酶抑制前列腺癌细胞的增殖、迁移与侵袭  

miR-485-5p Inhibits the Proliferation, Migration and Invasion of ProstateCancer Cells by Targeting OGT

作　　者：胡东来 赵梓岐 李元[1] 杨丽[2] 雷艳丽 楚元奎[1,3] HU Dong-Lai;ZHAO Zi-Qi;LI Yuan;YANG Li;LEI Yan-Li;CHU Yuan-Kui(Department of Laboratory Medicine,School of Clinical Medicine,Ningxia Medical University,Yinchuan 750004;Research Platform of Basic Medical School of Ningxia Medical University,Yinchuan 750004;Medical Experimental Center,General Hospital of Ningxia Medical University,Yinchuan 750004)

机构地区：[1]宁夏医科大学临床医学院检验学系,银川750004 [2]宁夏医科大学基础医学院科研平台,银川750004 [3]宁夏医科大学总医院医学实验中心,银川750004

出　　处：《中国生物化学与分子生物学报》2024年第2期258-268,共11页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目(No.82160465);宁夏自然科学基金项目(No.2021AAC03123)资助。

摘　　要：前列腺癌是男性生殖系统最常见的恶性肿瘤。尽管采用雄激素剥夺疗法等策略在一定程度上对治疗前列腺癌有效,但大多数患者最终会进展为临床尚无有效治疗手段的去势抵抗性前列腺癌。因此,寻找新的更加有效的前列腺癌治疗靶点就显得尤为关键。多项研究表明,微RNA(microRNAs,miRNAs)的异常表达与肿瘤的发生相关。已有报道显示,miRNA-485-5p(miR-485-5p)在多种肿瘤中发挥抑癌作用,但其在前列腺癌中的作用在较大程度上仍未可知。本研究旨在探究miR-485-5p在前列腺癌细胞增殖、迁移与侵袭的作用与机制。生物信息学预测和qRT-PCR检测发现,miR-485-5p在前列腺癌中表达下调。平板克隆形成实验、Transwell实验和划痕愈合实验证明,转染miR-485-5p模拟物显著抑制前列腺癌细胞的增殖、迁移与侵袭。生物信息学预测、双荧光素酶报告法、Western印迹和qRT-PCR检测证实,氧连接的N-乙酰氨基葡萄糖转移酶(O-linked N-acetylglucosamine transferase,OGT)是miR-485-5p的一个下游直接靶标。进一步的分析和检测显示,OGT在前列腺癌中呈高表达,转染OGT的siRNA能够显著抑制前列腺癌细胞的增殖、迁移与侵袭,同时有效逆转转染miR-485-5p抑制物所发挥的促癌作用。综上所述,miR-485-5p可以通过负向调控OGT进而抑制前列腺癌细胞的增殖、迁移与侵袭。本研究结果有助于进一步阐释miR-485-5p在前列腺癌中发生发展的作用和机制,可为寻找前列腺癌的治疗靶点提供实验依据。Prostate cancer is one of the most common malignant tumors of the male reproductive system.Although strategies such as androgen deprivation therapy are effective in treating prostate cancer,most patients will eventually progress to castration-resistant prostate cancer for which there is no clinically effective treatment.Therefore,it is particularly critical to find new and more effective therapeutic targets.Many studies have shown that the abnormal expression of microRNAs(miRNAs)is closely related to the occurrence of tumors.It has been reported that miRNA-485-5p(miR-485-5p)functions as a cancer suppressor in most tumors,but its role in prostate cancer remains largely unknown.This study aimed to explore the role and mechanism of miR-485-5p in the proliferation,migration and invasion of prostate cancer.Bioinformatics prediction and qRT-PCR detection showed that the expression of miR-485-5p was down-regulated in prostate cancer.Transfection of miR-485-5p mimics could inhibit the proliferation,migration and invasion of prostate cancer cells confirmed by plate cloning,Transwell and scratch healing experiments.Bioinformatics prediction,Western blotting and qRT-PCR detection confirmed that O-linked N-acetylglucosamine transferase(OGT)is a direct target of miR-485-5p.Further examination showed that OGT was highly expressed in prostate cancer,and transfection with OGT siRNA could significantly inhibit the proliferation,migration and invasion of prostate cancer cells and could effectively reverse the effect of miR-485-5p inhibitor.In summary,miR-485-5p can inhibit the proliferation,migration and invasion of prostate cancer cells by negatively regulating OGT.The results of this study are helpful to further elucidate the role and mechanism of miR-485-5p in the development and development of prostate cancer,and can provide experimental basis for searching for therapeutic targets of prostate cancer.

关 键 词：miR-485-5p 前列腺癌 氧连接的N-乙酰氨基葡萄糖转移酶 增殖 迁移 

分 类 号：Q527[生物学—生物化学]