青岛大学学报(医学版)2026,Vol.62Issue(3):400-406,7.DOI:10.11712/jms.2096-5532.2026.62.091
NEDD4调控RGS16表达对卵巢癌恶性行为及紫杉醇耐药影响
Effects of NEDD4-regulated RGS16 expression on malignant behavior and paclitaxel resistance of ovarian cancer
摘要
Abstract
Objective To investigate the effects of neural precursor cell expressed developmentally down-regulated protein 4(NEDD4)on the malignant behavior and paclitaxel(PTX)resistance of ovarian cancer(OC)by regulating the expression of regu-lator of G-protein signaling 16(RGS16).Methods Thirty cases of OC tissues(OC group)and corresponding adjacent tissues(Control group)were collected.Experimental cells were randomly divided into Blank,sh-NC/oe-NC,sh-RGS16,oe-NEDD4,oe-NEDD4+oe-RGS16,PTX,PTX+sh-NC/PTX+oe-NC,PTX+sh-RGS16,PTX+oe-NEDD4,and PTX+oe-NEDD4+oe-RGS16 groups.The mRNA and protein expression levels of RGS16 and NEDD4 were detected by RT-qPCR and Western blot.Cell proliferation and apoptosis were detected by CCK-8,5-ethynyl-2-deoxyuridine staining,and flow cytometry.Cell migration and in-vasion were detected by scratch and Transwell assays.The interaction between NEDD4 and RGS16 was analyzed by immunopreci-pitation,co-immunoprecipitation,and cycloheximide chase assays.Results Compared with the Control group,the OC group showed significantly increased mRNA and protein expression levels of RGS16(t=2.59,4.96,P<0.05).Compared with the sh-NC group,the sh-RGS16 group showed significantly decreased RGS16 expression,cell proliferation,migration,and invasion,and sig-nificantly increased apoptosis rate and sensitivity to PTX(t=4.24-10.78,P<0.05).Bioinformatics analysis suggested that NEDD4,as an E3 ubiquitin ligase,might degrade RGS16 by ubiquitination.Compared with the oe-NC group,the oe-NEDD4 group showed decreased RGS16 expression and inhibited malignant behavior of cells(F=5.85-36.50,P<0.05).Compared with the PTX group,the PTX+oe-NEDD4 group showed enhanced sensitivity to PTX and increased apoptosis rate(F=42.30,79.90,P<0.01);however,overexpression of RGS16 reversed these effects of NEDD4.Conclusion NEDD4 may inhibit the malignant progression of OC and reduce PTX resistance by degrading RGS16 through ubiquitination.关键词
卵巢肿瘤/Nedd4泛素蛋白连接酶类/RGS蛋白质类/细胞增殖/肿瘤浸润/紫杉醇/抗药性,肿瘤Key words
ovarian neoplasms/NEDD4 ubiquitin protein ligases/RGS proteins/cell proliferation/neoplasm invasiveness/paclitaxel/drug resistance,neoplasm分类
医药卫生引用本文复制引用
韩琛,高玉霞,何乾,辛丹丹,杨颖慧,王文翔..NEDD4调控RGS16表达对卵巢癌恶性行为及紫杉醇耐药影响[J].青岛大学学报(医学版),2026,62(3):400-406,7.基金项目
河南省医学科技攻关计划联合共建项目(LHGJ20210914) (LHGJ20210914)