The feedback loop between miR-222-3p and ZEB1 harnesses metastasis in renal cell carcinoma

被引：0

作者：

Fan Wang ^{[1
]}

Liao Li ^{[2
]}

Xiangfu Sun ^{[3
]}

Xianfu Cai ^{[4
]}

Jianjun Wang ^{[5
]}

Huiwen Luo ^{[6
]}

Yaodong Wang ^{[7
]}

Dong Ni ^{[8
]}

Decai Wang ^{[7
]}

机构：

[1] Department of Thyroid and Breast Surgery, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang

[2] Department of Child Healthcare, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang

[3] Department of Cardiothoracic Surgery, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang

[4] Department of Renal Transplantation, the First Affiliated Hospital of Xi’an Jiaotong University, Shaanxi Province, Xi’an

[5] Department of Hepatobiliary Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang

[6] NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang

[7] Department of Urology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang

[8] Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan

来源：

Cell Death Discovery | / 11卷 / 1期

基金：

中国国家自然科学基金;

关键词：

D O I：

10.1038/s41420-025-02385-0

中图分类号：

学科分类号：

摘要：

Renal cell carcinoma (RCC) is an aggressive malignancy originating from the renal parenchyma, often leading to high mortality due to local invasion and distant metastasis. MicroRNAs (miRNAs) play essential roles in RCC progression. Through miRNA sequencing, we identified significant upregulation of miR-222-3p in metastatic RCC tissues. Exosomes from highly metastatic RCC cells were found to transfer miR-222-3p to low-metastatic cells, enhancing their migration and invasion. Mechanistically, miR-222-3p directly targets the 3′ untranslated region (3′UTR) of the tumor-suppressor TRPS1, reducing its expression. TRPS1 downregulation releases its inhibitory effect on ZEB1, a key regulator of epithelial-mesenchymal transition (EMT), thereby promoting EMT and metastatic traits. ZEB1 further transactivates miR-222-3p, establishing a positive feedback loop. Additionally, miR-222-3p promotes a pre-metastatic niche by inducing M2 macrophage polarization, facilitating distant metastasis. These findings highlight miR-222-3p as a critical driver of RCC metastasis and suggest its potential as a diagnostic marker and therapeutic target for RCC. © The Author(s) 2025.

引用

共 50 条

[21] LncRNA TDRG1 promotes the metastasis of NSCLC cell through regulating miR-873-5p/ZEB1 axis [J].

Hu, Xiufeng ;

Mu, Yu ;

Wang, Jiaojie ;

Zhao, Yanqiu .

JOURNAL OF CELLULAR BIOCHEMISTRY, 2021, 122 (09) :969-982

[22] Negative feedback loop between p66Shc and ZEB1 regulates fibrotic EMT response in lung cancer cells [J].

Li, X. ;

Gao, D. ;

Wang, H. ;

Li, X. ;

Yang, J. ;

Yan, X. ;

Liu, Z. ;

Ma, Z. .

CELL DEATH & DISEASE, 2015, 6 :e1708-e1708

[23] Negative feedback loop between p66Shc and ZEB1 regulates fibrotic EMT response in lung cancer cells [J].

X Li ;

D Gao ;

H Wang ;

X Li ;

J Yang ;

X Yan ;

Z Liu ;

Z Ma .

Cell Death & Disease, 2015, 6 :e1708-e1708

[24] lncRNA TUG1-Mediated Mir-142-3p Downregulation Contributes to Metastasis and the Epithelial-to-Mesenchymal Transition of Hepatocellular Carcinoma by Targeting ZEB1 [J].

He, Chuan ;

Liu, Zhigang ;

Jin, Li ;

Zhang, Fang ;

Peng, Xinhao ;

Xiao, Yaqin ;

Wang, Xi ;

Lyu, Qian ;

Cai, XiaoJun .

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2018, 48 (05) :1928-1941

[25] Plasma Exosomal miR-146b-5p and miR-222-3p are Potential Biomarkers for Lymph Node Metastasis in Papillary Thyroid Carcinomas [J].

Jiang, Ke ;

Li, Genpeng ;

Chen, Wenjie ;

Song, Linlin ;

Wei, Tao ;

Li, Zhihui ;

Gong, Rixiang ;

Lei, Jianyong ;

Shi, Hubing ;

Zhu, Jingqiang .

ONCOTARGETS AND THERAPY, 2020, 13 :1311-1319

[26] miR-186 regulates epithelial-mesenchymal transformation to promote nasopharyngeal carcinoma metastasis by targeting ZEB1 [J].

Tang, Liangke ;

Xiang, Yalang ;

Zhou, Jing ;

Li, Tao ;

Jia, Tingting ;

Du, Guobo .

BRAZILIAN JOURNAL OF OTORHINOLARYNGOLOGY, 2024, 90 (01)

[27] miR-1236-3p represses the cell migration and invasion abilities by targeting ZEB1 in high-grade serous ovarian carcinoma [J].

Wang, Yu ;

Yan, Shi ;

Liu, Xiaolin ;

Zhang, Wenjing ;

Li, Yingwei ;

Dong, Ruifen ;

Zhang, Qing ;

Yang, Qifeng ;

Yuan, Cunzhong ;

Shen, Keng ;

Kong, Beihua .

ONCOLOGY REPORTS, 2014, 31 (04) :1905-1910

[28] KCNQ1OT1/miR-217/ZEB1 feedback loop facilitates cell migration and epithelial-mesenchymal transition in colorectal cancer [J].

Bian, Yinzhu ;

Gao, Guangyi ;

Zhang, Qun ;

Qian, Hanqing ;

Yu, Lixia ;

Yao, Ninghua ;

Qian, Jing ;

Liu, Baorui ;

Qian, Xiaoping .

CANCER BIOLOGY & THERAPY, 2019, 20 (06) :886-896

[29] PAX5-miR-142 feedback loop promotes breast cancer proliferation by regulating DNMT1 and ZEB1 [J].

Chen, Zhao-Hui ;

Chen, Yi-Bo ;

Yue, Hao-Ran ;

Zhou, Xue-Jie ;

Ma, Hai-Yan ;

Wang, Xin ;

Cao, Xu-Chen ;

Yu, Yue .

MOLECULAR MEDICINE, 2023, 29 (01)

[30] PAX5-miR-142 feedback loop promotes breast cancer proliferation by regulating DNMT1 and ZEB1 [J].

Zhao-Hui Chen ;

Yi-Bo Chen ;

Hao-Ran Yue ;

Xue-Jie Zhou ;

Hai-Yan Ma ;

Xin Wang ;

Xu-Chen Cao ;

Yue Yu .

Molecular Medicine, 29

← 1 2 3 4 5 →