Article Data

  • Views 313
  • Dowloads 129

Original Research

Open Access

GINS2 regulates epithelial mesenchymal transformation and cell cycle in endometrial carcinoma by stimulating ERK/MAPK signaling

  • Min Zhou1,*,
  • Wei Hua1
  • Yulan Sun1

1Department of Pathology, The First Affiliated Hospital of Harbin Medical University, 150001 Harbin, Heilongjiang, China

DOI: 10.22514/ejgo.2023.067 Vol.44,Issue 4,August 2023 pp.156-163

Submitted: 07 June 2023 Accepted: 07 July 2023

Published: 15 August 2023

*Corresponding Author(s): Min Zhou E-mail:


Endometrial cancer (EC) is one of the three main gynecological cancers. Identifying new therapeutic targets and further elucidating the molecular mechanisms of EC tumorigenesis have important implications for women’s health. The Go-Ichi-Ni-San (GINS) family, which includes four subunits (GINS1–4), has specific functions in DNA replication and cell cycle. The Cancer Genome Atlas (TCGA) data showed that GINS2 transcription level is upregulated in endometrial cancer tissue. However, the possible role of GINS2 in EC progression is still unknown. Herein, we explored the role of GINS2 in EC. We noticed that GINS2 was overexpressed in EC cells. GINS2 knockdown suppressed the proliferation of EC cells and induced cell cycle arrest. We further noticed that GINS2 knockdown restrained the Epithelial mesenchymal transformation (EMT) of EC cells. Mechanically, its downregulation suppressed the extracellular regulated protein kinase (ERK)/Microtubule-Associated Protein Kinase (MAPK) pathway, thereby suppressing EC progression. Thus, GINS2 has the potential to act as a therapeutic target for EC.


Endometrial cancer (EC); GINS2; Cell cycle; EMT; ERK/MAPK pathway

Cite and Share

Min Zhou,Wei Hua,Yulan Sun. GINS2 regulates epithelial mesenchymal transformation and cell cycle in endometrial carcinoma by stimulating ERK/MAPK signaling. European Journal of Gynaecological Oncology. 2023. 44(4);156-163.


[1] Pecorino B, Lagana AS, Chiantera V, Ferrara M, Di Stefano AB, Di Donna MC, et al. Progression free survival, overall survival, and relapse rate in endometrioid ovarian cancer and synchronous endometrial-ovarian endometrioid cancer (SEO-EC): results from a large retrospective analysis. Medicina. 2022; 58: 1706.

[2] Goel P, Singh V, Sharma R, Chaudhary D, Chatterjee A, Dora T, et al. Early endometrial carcinoma: experience and outcomes. Journal of Cancer Research and Therapeutics. 2023; 19: S0.

[3] Camilloni A, Nati G, Maggiolini P, Romanelli A, Latina R, Carbone G, et al. Chronic non-cancer pain in primary care: an Italian cross-sectional study. Signa Vitae. 2021; 17: 54–62.

[4] Kluska A, Tomasik B, Moszynska-Zielinska M, Zytko L, Tracz N, Spych M, et al. Prospective analysis of the impact of adjuvant treatment with external beam radiation therapy and vaginal brachytherapy on health-related quality of life in patients with early-stage endometrioid endometrial carcinoma. To be published in Ginekologia Polska. 2023.[Preprint].

[5] Yan T, Liang W, Jiang E, Ye A, Wu Q, Xi M. GINS2 regulates cell proliferation and apoptosis in human epithelial ovarian cancer. Oncology Letters. 2018; 16: 2591–2598.

[6] Huang L, Chen S, Fan H, Ji D, Chen C, Sheng W. GINS2 promotes EMT in pancreatic cancer via specifically stimulating ERK/MAPK signaling. Cancer Gene Therapy. 2021; 28: 839–849.

[7] Liu X, Sun L, Zhang S, Zhang S, Li W. GINS2 facilitates epithe-lial‐to‐mesenchymal transition in non-small-cell lung cancer through modulating PI3K/Akt and MEK/ERK signaling. Journal of Cellular Physiology. 2020; 235: 7747–756.

[8] Shan DD, Zheng QX, Chen Z. Go-Ichi-Ni-San 2: a potential biomarker and therapeutic target in human cancers. World Journal of Gastrointestinal Oncology. 2022; 14: 1892–1902.

[9] Zhang K, Zhou J, Wu T, Tian Q, Liu T, Wang W, et al. Combined analysis of expression, prognosis and immune infiltration of GINS family genes in human sarcoma. Aging. 2022; 14: 5895–5907.

[10] Králíčková M, Vetvicka V, Laganà AS. Endometrial cancer—is our knowledge changing? Translational Cancer Research. 2020; 9: 7734–7745.

[11] Sponholtz TR, Palmer JR, Rosenberg L, Chen C, Chen Y, Clarke MA, et al. Risk factors for endometrial cancer in Black women. Cancer Causes & Control. 2023; 34: 421–430.

[12] Pitakkarnkul S, Chanpanitkitchot S, Tangjitgamol S. Management of inoperable endometrial cancer. Obstetrics & Gynecology Science. 2022; 65: 303–316.

[13] Mutch DG. Targeted therapy in endometrial cancer: making progress. Cancer. 2016; 122: 3428–3429.

[14] He S, Zhang M, Ye Y, Song Y, Ma X, Wang G, et al. GINS2 affects cell proliferation, apoptosis, migration and invasion in thyroid cancer via regulating MAPK signaling pathway. Molecular Medicine Reports. 2021; 23: 246.

[15] Li Z, Song G, Guo D, Zhou Z, Qiu C, Xiao C, et al. Identification of GINS2 prognostic potential and involvement in immune cell infiltration in hepatocellular carcinoma. Journal of Cancer. 2022; 13: 610–622.

[16] Meng W, Jiang Z, Zhang X, Cai B, Ma L, Guan Y. Comprehensive pan-cancer analysis of GINS2 for human tumour prognosis and as an immunological biomarker. Computational and Mathematical Methods in Medicine. 2022; 2022: 3119721.

[17] 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.

[18] Ren B, Zheng Y, Nie L, Wu F, Huang L, Wei J, et al. GINS2 promotes osteosarcoma tumorigenesis via STAT3/MYC axis. Journal of Oncology. 2023; 2023: 8454142.

[19] Wang C, Wang H, Zheng C, Li B, Liu Z, Zhang L, et al. Discovery of Coumarin-based MEK1/2 PROTAC effective in human cancer cells. ACS Medicinal Chemistry Letters. 2022; 14: 92–102.

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