CCZ1 Accelerates the Progression of Cervical Squamous Cell Carcinoma by Promoting MMP2/MMP17 Expression

被引：0

作者：

Yu, Jing ^{[1
,2
]}

Yuan, Zhenlong ^{[1
]}

Liu, Jing ^{[1
]}

Deng, Lu ^{[1
]}

Zhao, Yuting ^{[1
]}

Wang, Shengnan ^{[1
]}

Tang, Enyu ^{[1
]}

Yang, Xi ^{[1
]}

Li, Ning ^{[1
]}

An, Jusheng ^{[1
]}

Wu, Lingying ^{[1
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, Canc Hosp, Dept Gynecol Oncol, Natl Clin Res Ctr Canc,Natl Canc Ctr, Beijing 100021, Peoples R China

[2] Chinese Acad Med Sci & Peking Union Med Coll, Canc Hosp, State Key Lab Mol Oncol, Natl Clin Res Ctr Canc,Natl Canc Ctr, Beijing 100021, Peoples R China

来源：

BIOMEDICINES | 2024年 / 12卷 / 07期

基金：

中国国家自然科学基金;

关键词：

CCZ1; cervical squamous cell carcinoma; MMP2; MMP17; MATRIX METALLOPROTEINASES; CANCER; MORTALITY;

D O I：

10.3390/biomedicines12071468

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cervical squamous cell carcinoma (CSCC) represents a significant global health concern among females. Identifying new biomarkers and therapeutic targets is pivotal for improving the prognosis of CSCC. This study investigates the prognostic relevance of CCZ1 in CSCC and elucidates its downstream pathways and targets using a combination of bioinformatics analysis and experimental validation. Transcriptomic analysis of 239 CSCC and 3 normal cervical samples from The Cancer Genome Atlas database reveals a marked upregulation of CCZ1 mRNA levels in CSCC, and elevated CCZ1 mRNA levels were associated with poor prognosis. Immunohistochemical analysis of clinical samples also confirmed these findings. Furthermore, functional assays, including Cell Counting Kit-8, colony formation, Transwell, and flow cytometry, elucidated the influence of CCZ1 on CSCC cell proliferation, migration, invasion, and cell cycle progression. Remarkably, CCZ1 knockdown suppressed CSCC progression both in vitro and in vivo. Mechanistically, CCZ1 knockdown downregulated MMP2 and MMP17 expression. Restoring MMP2 or MMP17 expression rescued phenotypic alterations induced by CCZ1 knockdown. Hence, CCZ1 promotes CSCC progression by upregulating MMP2 and MMP17 expression, emerging as a novel biomarker in CSCC and presenting potential as a therapeutic target in CSCC.

引用

页数：20

共 44 条

[1] Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis [J].

Arbyn, Marc ;

Weiderpass, Elisabete ;

Bruni, Laia ;

de Sanjose, Silvia ;

Saraiya, Mona ;

Ferlay, Jacques ;

Bray, Freddie .

LANCET GLOBAL HEALTH, 2020, 8 (02) :E191-E203

[2] An updated patent review of matrix metalloproteinase (MMP) inhibitors (2021-present) [J].

Banerjee, Suvankar ;

Baidya, Sandip Kumar ;

Adhikari, Nilanjan ;

Jha, Tarun .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2023, 33 (10) :631-649

[3] Regulatory sites in the Mon1-Ccz1 complex control Rab5 to Rab7 transition and endosome maturation [J].

Borchers, Ann-Christin ;

Janz, Maren ;

Schaefer, Jan-Hannes ;

Moeller, Arne ;

Kuemmel, Daniel ;

Paululat, Achim ;

Ungermann, Christian ;

Langemeyer, Lars .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2023, 120 (30)

[4] Enhancing autophagy maturation with CCZ1-MON1A complex alleviates neuropathology and memory defects in Alzheimer disease models [J].

Cai, Cui-Zan ;

Zhuang, Xu-Xu ;

Zhu, Qi ;

Wu, Ming-Yue ;

Su, Huanxing ;

Wang, Xiao-Jin ;

Iyaswamy, Ashok ;

Yue, Zhenyu ;

Wang, Qian ;

Zhang, Bin ;

Xue, Yu ;

Tan, Jieqiong ;

Li, Min ;

He, Huanhuan ;

Lu, Jia-Hong .

THERANOSTICS, 2022, 12 (04) :1738-1755

[5] Inhibition of MMPs supports amoeboid angiogenesis hampering VEGF-targeted therapies via MLC and ERK 1/2 signaling [J].

Chilla, Anastasia ;

Anceschi, Cecilia ;

Frediani, Elena ;

Scavone, Francesca ;

Del Rosso, Tommaso ;

Pelagio, Giuseppe ;

Tufaro, Antonio ;

De Palma, Giuseppe ;

Del Rosso, Mario ;

Fibbi, Gabriella ;

Chiarugi, Paola ;

Laurenzana, Anna ;

Margheri, Francesca .

JOURNAL OF TRANSLATIONAL MEDICINE, 2023, 21 (01)

[6] Matrix metalloproteinases in the CNS: interferons get nervous [J].

Chopra, Sameeksha ;

Overall, Christopher M. ;

Dufour, Antoine .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2019, 76 (16) :3083-3095

[7] Body weight regulation via MT1-MMP-mediated cleavage of GFRAL [J].

Chow, Chi Fung Willis ;

Guo, Xuanming ;

Asthana, Pallavi ;

Zhang, Shuo ;

Wong, Sheung Kin Ken ;

Fallah, Samane ;

Che, Sijia ;

Gurung, Susma ;

Wang, Zening ;

Lee, Ki Baek ;

Ge, Xin ;

Yuan, Shiyang ;

Xu, Haoyu ;

Ip, Jacque Pak Kan ;

Jiang, Zhixin ;

Zhai, Lixiang ;

Wu, Jiayan ;

Zhang, Yijing ;

Mahato, Arun Kumar ;

Saarma, Mart ;

Lin, Cheng Yuan ;

Kwan, Hiu Yee ;

Huang, Tao ;

Lyu, Aiping ;

Zhou, Zhongjun ;

Bian, Zhao-Xiang ;

Wong, Hoi Leong Xavier .

NATURE METABOLISM, 2022, 4 (02) :203-+

[8] Racial and Ethnic Disparities in Cervical Cancer Incidence, Survival, and Mortality by Histologic Subtype [J].

Cohen, Camryn M. ;

Wentzensen, Nicolas ;

Castle, Philip E. ;

Schiffman, Mark ;

Zuna, Rosemary ;

Arend, Rebecca C. ;

Clarke, Megan A. .

JOURNAL OF CLINICAL ONCOLOGY, 2023, 41 (05) :1059-+

[9] The matrix in cancer [J].

Cox, Thomas R. .

NATURE REVIEWS CANCER, 2021, 21 (04) :217-238

[10] Matrix Metalloproteinases: From Molecular Mechanisms to Physiology, Pathophysiology, and Pharmacology [J].

de Almeida, Luiz G. N. ;

Thode, Hayley ;

Eslambolchi, Yekta ;

Chopra, Sameeksha ;

Young, Daniel ;

Gill, Sean ;

Devel, Laurent ;

Dufour, Antoine .

PHARMACOLOGICAL REVIEWS, 2022, 74 (03) :712-768

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