Article Data

  • Views 473
  • Dowloads 140

Original Research

Open Access

Overexpression of USP43 induces the growth and stem cell-like properties of cervical cancer by activating ERK1/2 through ZEB1

  • Qiaoling Xu1
  • Xiaoli Li1,*,

1Internal Medicine Oncology, Minhang Branch, Fudan University Shanghai Cancer Center, 200240 Shanghai, China

DOI: 10.22514/ejgo.2023.089 Vol.44,Issue 5,October 2023 pp.140-147

Submitted: 04 July 2023 Accepted: 04 August 2023

Published: 15 October 2023

*Corresponding Author(s): Xiaoli Li E-mail:


Cervical cancer (CC) is the most common type of gynecological malignancy in women, and targeting stem cells and inhibiting tumor stem cell-like properties of CC remains an important field of research as an attempt to improve treatment outcomes. This study focused on Ubiquitin-specific-processing Protease 43 (USP43), a member of the deubiquitinase (DUBs) family known to play a role in tumor progression, and analysis of the The Cancer Genome Atlas (TCGA) data and survival computations revealed that USP43 was highly expressed in CC and correlated with poor prognosis. However, the role of USP43 in CC has been under-reported, and its underlying mechanism remains unclear. To investigate the effect and mechanism of USP43, its expression in CC cells and tissues were examined, and the results showed that it was significantly upregulated. Subsequently, knockdown experiments revealed that reducing USP43 expression suppressed CC cell proliferation, and depleting USP43 inhibited the stem cell-like properties of CC cells and impaired their migration abilities. Further investigations indicated that USP43 promoted Zinc finger E-box binding protein 1 (ZEB1)-induced activation of Extracellular regulatory kinase 1/2 (ERK1/2) signaling in CC. Based on these findings, we propose that USP43 could serve as a promising target for CC.


Cervical cancer (CC); USP43; ZEB1; ERK1/2; Stem cell-like properties

Cite and Share

Qiaoling Xu,Xiaoli Li. Overexpression of USP43 induces the growth and stem cell-like properties of cervical cancer by activating ERK1/2 through ZEB1. European Journal of Gynaecological Oncology. 2023. 44(5);140-147.


[1] Stevens MJ, Ko F, Martland J, Brown R, Bell L, Atyeo J, et al. Safety and efficacy of single insertion accelerated MR-image guided brachytherapy following chemo-radiation in locally advanced cervix cancer: modifying our EMBRACE during the COVID pandemic. Radiation Oncology. 2023; 18: 54.

[2] Lin S, Wang M, Cao QQ, Li Q. Chromatin modified protein 4C (CHMP4C) facilitates the malignant development of cervical cancer cells. FEBS Open Bio. 2020; 10: 1295–1303.

[3] Ouyang F, Liu J, Xia M, Lin C, Wu X, Ye L, et al. GINS2 is a novel prognostic biomarker and promotes tumor progression in early-stage cervical cancer. Oncology Reports. 2021; 45: 65.

[4] Wang P, Chen C, Zhang QH, Sun GD, Wang CA, Li W. Retraction of lumbar disc herniation achieved by noninvasive techniques: a case report. World Journal of Clinical Cases. 2021; 9: 8082–8089.

[5] Liu L, Huan L, Zhang Y, Wei W, Chen Z, Xu D, et al. Ubiquitin-specific protease 8 inhibits lipopolysaccharide-triggered pyroptosis of human bronchial epithelial cells by regulating PI3K/AKT and NF-κB pathways. Allergologia et Immunopathologia. 2022; 50: 96–103.

[6] Cui N, Li L, Feng Q, Ma HM, Lei D, Zheng PS. Hexokinase 2 promotes cell growth and tumor formation through the Raf/MEK/ERK signaling pathway in cervical cancer. Frontiers in Oncology. 2020; 10: 581208.

[7] Sharma A, Kaur H, De R, Srinivasan R, Pal A, Bhattacharyya S. Knockdown of E-cadherin induces cancer stem-cell-like phenotype and drug resistance in cervical cancer cells. Biochemistry and Cell Biology. 2021; 99: 587–595.

[8] Lin F, Xie Z, Chang L, Li W, Wang L, Hou Y, et al. USP43 promotes tumorigenesis through regulating cell cycle and EMT in breast cancer. International Journal of Clinical and Experimental Pathology. 2017; 10: 11014–11021.

[9] Ye DX, Wang SS, Huang Y, Wang XJ, Chi P. USP43 directly regulates ZEB1 protein, mediating proliferation and metastasis of colorectal cancer. Journal of Cancer. 2021; 12: 404–416.

[10] Lavaud M, Mullard M, Tesfaye R, Amiaud J, Legrand M, Danieau G, et al. Overexpression of the ubiquitin specific proteases USP43, USP41, USP27x and USP6 in osteosarcoma cell lines: inhibition of osteosarcoma tumor growth and lung metastasis development by the USP antagonist PR619. Cells. 2021; 10: 2268.

[11] Sun Q, Zhang H, Zong L, Julaiti A, Jing X, Zhang L. Prognostic value and oncogenic effects of ubiquitin-specific protease 43 in lung squamous cell carcinoma. The Tohoku Journal of Experimental Medicine. 2022; 257: 135–145.

[12] Hou S, Zhang X, Yang J. Long non-coding RNA ABHD11-AS1 facilitates the progression of cervical cancer by competitively binding to miR-330-5p and upregulating MARK2. Experimental Cell Research. 2022; 410: 112929.

[13] Luan Y, Jiang L, Luan Y, Xie Y, Yang Y, Ren KD. Mitophagy and traumatic brain injury: regulatory mechanisms and therapeutic potentials. Oxidative Medicine and Cellular Longevity. 2023; 2023: 2023:1649842.

[14] Zhang L, Alimu G, Du Z, Yan T, Li H, Ma R, et al. Functionalized magnetic nanoparticles for NIR-induced photothermal therapy of potential application in cervical cancer. ACS Omega. 2023; 8: 21793–21801.

[15] Rey Valzacchi GM, Odetto D, Saadi JM, Zamora LB, Loza C, Medina M, et al. Conservative treatment of cervical cancer: a single center experience over a two-decade period. Gynecologic Oncology Reports. 2023; 48: 101226.

[16] Zhao Z, Lin Z, Guo X, Al-danakh A, He H, Qin H, et al. Ubiquitin-specific protease 43 impacts pancreatic ductal adenocarcinoma prognosis by altering its proliferation and infiltration of surrounding immune cells. Journal of Immunology Research. 2023; 2023: 4311388.

[17] Lin Z, Huang J, Zhu L, Lin X, Huang Y, Chen C, et al. TRIM9 interacts with ZEB1 to suppress esophageal cancer by promoting ZEB1 protein degradation via the UPP pathway. BioMed Research International. 2023; 2023: 2942402.

[18] Wu C, Hou X, Li S, Luo S. Long noncoding RNA ZEB1-AS1 attenuates ferroptosis of gastric cancer cells through modulating miR-429/BGN axis. Journal of Biochemical and Molecular Toxicology. 2023; 37: e23381.

[19] Han Y, Luo Y, Wang Y, Chen Y, Li M, Jiang Y. Hepatocyte growth factor increases the invasive potential of PC-3 human prostate cancer cells via an ERK/MAPK and Zeb-1 signaling pathway. Oncology Letters. 2016; 11: 753–759.

[20] Lang SJ, Schmiech M, Hafner S, Paetz C, Werner K, El Gaafary M, et al. Chrysosplenol D, a flavonol from Artemisia annua, induces ERK1/2-mediated apoptosis in triple negative human breast cancer cells. International Journal of Molecular Sciences. 2020; 21: 4090.

[21] Li B, Xiao Q, Shan L, Song Y. NCAPH promotes cell proliferation and inhibits cell apoptosis of bladder cancer cells through MEK/ERK signaling pathway. Cell Cycle. 2022; 21: 427–438.

[22] Gao Y, Li H, Han Q, Li Y, Wang T, Huang C, et al. Overexpression of DUSP6 enhances chemotherapy-resistance of ovarian epithelial cancer by regulating the ERK signaling pathway. Journal of Cancer. 2020; 11: 3151–3164.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.

JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Submission Turnaround Time