SMURF2 Inhibits Autophagy and Growth in Ovarian Cancer by Regulating the RACK1/AKT/mTOR Pathway

IF 2.4 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology Pub Date : 2025-08-18 DOI:10.1111/aji.70140

Lei Wu, Ziyi Xiao, Siyue Zhang, Li Guo, Xiaojian Liu, Lihua Zhang, Jingjing Xu, Mengmeng Lv, Jinhua Wang

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引用次数: 0

Abstract

Background

Ovarian cancer (OC) is a common malignancy characterized by disseminated peritoneal metastases. Smad ubiquitin regulatory factor 2 (SMURF2) is involved in OC progression by stabilizing receptor for activated C kinase 1 (RACK1). However, the functions and mechanisms of action of SMURF2 in OC remain unclear. This biological function of SMURF2 in OC and its potential mechanisms of action were investigated in this study.

Methods

The expression of SMURF2 in ovarian tumor tissues, patient serum, and OC cell lines was determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and/or western blotting. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays, flow cytometry, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) were used for detecting cell proliferation and apoptosis. Autophagosomes in SKOV3 cells were observed using transmission electron microscopy. Immunohistochemistry and RT-qPCR were performed to evaluate SMURF2 expression. The levels of proteins related to autophagy and RACK1 were measured using western blotting and RT-qPCR, respectively. Western blotting was performed to assess the expression of AKT/mTOR pathway-related proteins.

Results

SMURF2 was underexpressed in OC tissues and cell lines compared with that in adjacent normal tissues or normal ovarian epithelial cells. RT-qPCR results suggested that SMURF2 was downregulated in the serum of patients with OC. SMURF2 overexpression inhibited SKOV3 cell growth and autophagy, and induced apoptosis both in vitro and in vivo. Moreover, SMURF2 overexpression suppressed RACK1 expression in SKOV3 cells. The AKT/mTOR pathway was activated by SMURF2 overexpression in SKOV3, and OC cells and tissues.

Conclusions

SMURF2 plays a key role in OC by inhibiting cell autophagy and growth via activation of the RACK1/AKT/mTOR pathway, which might potentially be a new biomarker for OC diagnosis and therapy.

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SMURF2通过调控RACK1/AKT/mTOR通路抑制卵巢癌自噬和生长

卵巢癌（OC）是一种常见的恶性肿瘤，以播散性腹膜转移为特征。Smad泛素调节因子2 （SMURF2）通过稳定活化C激酶1 （RACK1）受体参与OC的进展。然而，SMURF2在OC中的功能和作用机制尚不清楚。本研究探讨了SMURF2在OC中的生物学功能及其潜在的作用机制。方法采用逆转录-定量聚合酶链反应（RT-qPCR）和/或western blotting检测SMURF2在卵巢肿瘤组织、患者血清和卵巢癌细胞株中的表达。采用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基- 2h -溴化四唑（MTT）检测、流式细胞术、末端脱氧核苷酸转移酶dUTP镍端标记（TUNEL）检测细胞增殖和凋亡。透射电镜观察SKOV3细胞的自噬体。免疫组织化学和RT-qPCR检测SMURF2的表达。采用western blotting和RT-qPCR分别检测自噬和RACK1相关蛋白的水平。Western blotting检测AKT/mTOR通路相关蛋白的表达。结果SMURF2在卵巢癌组织和细胞系中的表达低于相邻正常组织和正常卵巢上皮细胞。RT-qPCR结果显示，OC患者血清中SMURF2表达下调。SMURF2过表达抑制SKOV3细胞生长和自噬，诱导细胞凋亡。此外，SMURF2过表达抑制了RACK1在SKOV3细胞中的表达。SMURF2在SKOV3和OC细胞和组织中过表达激活AKT/mTOR通路。结论SMURF2通过激活RACK1/AKT/mTOR通路抑制细胞自噬和生长，在OC中发挥关键作用，可能成为OC诊断和治疗的新生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

American Journal of Reproductive Immunology 医学-免疫学

CiteScore

6.20

自引率

5.60%

发文量

314

审稿时长

2 months

期刊介绍： The American Journal of Reproductive Immunology is an international journal devoted to the presentation of current information in all areas relating to Reproductive Immunology. The journal is directed toward both the basic scientist and the clinician, covering the whole process of reproduction as affected by immunological processes. The journal covers a variety of subspecialty topics, including fertility immunology, pregnancy immunology, immunogenetics, mucosal immunology, immunocontraception, endometriosis, abortion, tumor immunology of the reproductive tract, autoantibodies, infectious disease of the reproductive tract, and technical news.