PNN促进肾癌的发展并抑制舒尼替尼诱导的细胞凋亡(英文)  

Pinin Contributes to ccRCC Progression and Resistance to Sunitinib-Induced Apoptosis

作　　者：余肖 刘开泰[2] 项振飞[2] 林晨 张雁儒 王萍[1] 马琪[3] YU Xiao;LIU Kaitai;XIANG Zhenfei;LIN Chen;ZHANG Yanru;WANG Ping;MA Qi(Zhejiang Provincial Key Laboratory of Pathophysiology,Ningbo University School of Medicine,Ningbo 315211,China;Department of Radiation Oncology,Ningbo Medical Center Lihuili Hospital,Ningbo 315040,China;Translational Research Laboratory for Urology,the Key Laboratory of Ningbo City,Ningbo First Hospital,Ningbo 315010,China)

机构地区：[1]宁波大学医学院,浙江省病理生理重点实验室,宁波315211 [2]宁波市医疗中心李惠利医院放疗科,宁波315040 [3]宁波市第一医院宁波市泌尿系疾病转化医学研究实验室,宁波315010

出　　处：《中国细胞生物学学报》2020年第9期1560-1569,共10页Chinese Journal of Cell Biology

基　　金：宁波市自然科学基金(批准号:2017A610185);浙江省医药卫生科技计划项目(批准号:2019KY188);宁波市医学科技计划项目(批准号:2018A01);宁波大学王宽诚幸福基金资助的课题。

摘　　要：桥粒相关蛋白与肿瘤的关系是目前的研究热点之一。传统观点认为,桥粒相关蛋白PNN(pinin)能够促进上皮细胞间的黏附和RNA的选择性剪接;而新近研究发现,PNN在肝癌、乳腺癌等肿瘤的发生发展中扮演着重要角色;但其是否参与肾透明细胞癌(ccRCC)的发生,尚需深入研究。在该研究中,首先发现PNN在肾癌组织和细胞中的表达显著性高于对照组;且其升高程度与肾癌的病理分级密切相关。其次,降低肾癌细胞中PNN的表达后,细胞增殖被显著抑制,细胞周期被阻滞在G0/G1期。最后,降低细胞内PNN的表达能显著增强靶向药物舒尼替尼的细胞毒性,增加凋亡细胞的数量,此作用与PI3K/AKT途径密切相关。因此,PNN能激活PI3K/AKT通路促进靶向药物舒尼替尼对肾癌细胞的毒性作用;PNN有望成为肾癌耐药靶向治疗的潜在靶点。The expression and bio-function of desomosome-related proteins have been gradually disclosed in various human cancers.PNN(pinin)is a desmosome-associated molecule that has been well studied in epithelial cell-cell adhesion and RNA alternative splicing,which suggests its involvement in cancer progression.However,little is known about the association between PNN expression and ccRCC(clear cell renal cancer cell)tumorigenesis.This study reported that the expression of PNN was significantly increased in ccRCC tissues and cells,and the elevated level of PNN was closely associated with pathological grade of patients with ccRCC.Suppression of PNN expression inhibited cell proliferation and cell viability,inducing G0/G1 cell cycle arrests.Furthermore,si-PNN treatment significantly enhanced the cytotoxic effect of sunitinib and the apoptotic cell number compared with cells underwent sunitinib treatment only.The molecular signals for this phenomenon involved the PNN-mediated activation of PI3K/AKT pathway.In conclusion,these results reveals that PNN contributes to ccRCC progression and resistance to targeted drug-induced apoptosis via maintaining PI3K/AKT activation and may become a potential therapeutic target for ccRCC.

关 键 词：桥粒相关蛋白PNN 细胞增殖 舒尼替尼 肾透明细胞癌 

分 类 号：R737.11[医药卫生—肿瘤]