Article Data

  • Views 572
  • Dowloads 114

Original Research

Open Access

CDCA2 promotes breast cancer progression by downregulating KISS1 expression

  • Yi Luo1,*,
  • Zeyu Hou1
  • Guoli Feng1
  • Daigang Xiong1
  • Jing Chen2

1Department of Surgery of Thyroid and Breast, Affiliated Hospital of Zunyi Medical University, 563000 Zunyi, Guizhou, China

2Center of Physical Examination, Affiliated Hospital of Zunyi Medical University, 563000 Zunyi, Guizhou, China

DOI: 10.22514/ejgo.2024.034 Vol.45,Issue 2,April 2024 pp.127-134

Submitted: 03 July 2023 Accepted: 27 September 2023

Published: 15 April 2024

*Corresponding Author(s): Yi Luo E-mail:


Breast cancer is a females’ prevalent malignancy, resulting in higher mortality rates than other cancers. Therefore, exploring effective therapeutic targets and diagnostic biomarkers is critical for improving drugs’ curative effect in treating breast cancer patients. The MDA-MB-231 and Michigan Cancer Foundation-7 (MCF-7) cells were transfected by pc-CDCA2, Small interfering RNA Negative Control (siNC), siCDCA2, and pc-KISS1 to investigate the effects of cell division cycle associated 2 (CDCA2) and kisspeptin 1 (KISS1) protein on breast cancer cell’s viability, migration and invasion. Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) was used to examine the CDCA2 mRNA expression. Impact of CDCA2 and KISS1 on invasion ability, motility and viability of breast cancer cells were detected via colony-forming unit, Cell Counting Kit-8 (CCK-8) and transwell assay. The Annexin V-Fluorescein Isothiocyanate (annexin V-FITC) staining was employed to determine the cellular apoptosis ratio based on flow cytometry. Findings indicated that CDCA2 expression got increased in breast cancer tissues, which greatly enhanced the cell proliferation, migration and invasion ability. Moreover, the regulation of CDCA2 may suppress the activation of KISS1 in breast cancer cells. In summary, the findings depicted that in breast cancer cells, the CDCA2 expression was enhanced to promote cells motility, invasiveness and viability through inhibition of KISS1 expression. Therefore, targeted gene therapy to suppress the expression levels of CDCA2 and upregulation of the KISS1 have the potential to be promising therapeutic strategies for treating breast cancer metastasis.


CDCA2; KISS1; Breast cancer; Apoptosis; Metastasis

Cite and Share

Yi Luo,Zeyu Hou,Guoli Feng,Daigang Xiong,Jing Chen. CDCA2 promotes breast cancer progression by downregulating KISS1 expression. European Journal of Gynaecological Oncology. 2024. 45(2);127-134.


[1] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2018; 68: 394–424.

[2] Tao Z, Shi A, Lu C, Song T, Zhang Z, Zhao J. Breast cancer: epidemiology and etiology. Cell Biochemistry and Biophysics. 2015; 72: 333–338.

[3] DeSantis CE, Fedewa SA, Goding Sauer A, Kramer JL, Smith RA, Jemal A. Breast cancer statistics, 2015: convergence of incidence rates between black and white women. CA: A Cancer Journal for Clinicians. 2016; 66: 31–42.

[4] Qian C, Guan M, Si C, Shen H, Jin T, Zhang T. Identification of differentially expressed profiles of lncRNAs and mRNAs in ER-negative and HER-2 positive breast cancer. Archives of Medical Science—Civilization Diseases. 2017; 2: 148–160.

[5] Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. The New England Journal of Medicine. 2016; 375: 1738–1748.

[6] Lu P, Cheng W, Fang K, Yu B. Multidimensional study of cell division cycle-associated proteins with prognostic value in gastric carcinoma. Bosnian Journal of Basic Medical Sciences. 2022; 22: 64–76.

[7] Thang PM, Takano A, Yoshitake Y, Shinohara M, Murakami Y, Daigo Y. Cell division cycle associated 1 as a novel prognostic biomarker and therapeutic target for oral cancer. International Journal of Oncology. 2016; 49: 1385–1393.

[8] Meng J, Gao L, Zhang M, Gao S, Fan S, Liang C. Systematic investigation of the prognostic value of cell division cycle-associated proteins for clear cell renal cell carcinoma patients. Biomarkers in Medicine. 2020; 14: 223–238.

[9] Phan NN, Wang C, Li K, Chen C, Chiao C, Yu H, et al. Distinct expression of CDCA3, CDCA5, and CDCA8 leads to shorter relapse free survival in breast cancer patient. Oncotarget. 2018; 9: 6977–6992.

[10] Xu Y, Wu X, Li F, Huang D, Zhu W. CDCA4, a downstream gene of the Nrf2 signaling pathway, regulates cell proliferation and apoptosis in the MCF‑7/ADM human breast cancer cell line. Molecular medicine reports. 2018; 17: 1507–1512.

[11] Fu G, Xu Z, Chen X, Pan H, Wang Y, Jin B. CDCA5 functions as a tumor promoter in bladder cancer by dysregulating mitochondria-mediated apoptosis, cell cycle regulation and PI3k/AKT/mTOR pathway activation. Journal of Cancer. 2020; 11: 2408–2420.

[12] Zhang Y, Cheng Y, Zhang Z, Bai Z, Jin H, Guo X, et al. CDCA2 inhibits apoptosis and promotes cell proliferation in prostate cancer and is directly regulated by HIF-1α pathway. Frontiers in Oncology. 2020; 10: 725.

[13] Platonov ME, Borovjagin AV, Kaverina N, Xiao T, Kadagidze Z, Lesniak M, et al. KISS1 tumor suppressor restricts angiogenesis of breast cancer brain metastases and sensitizes them to oncolytic virotherapy in vitro. Cancer Letters. 2018; 417: 75–88.

[14] Martin TA, Watkins G, Jiang WG. KiSS-1 expression in human breast cancer. Clinical & Experimental Metastasis. 2005; 22: 503–511.

[15] Corno C, Perego P. KiSS1 in regulation of metastasis and response to antitumor drugs. Drug Resistance Updates. 2019; 42: 12–21.

[16] Ulasov IV, Borovjagin AV, Timashev P, Cristofanili M, Welch DR. KISS1 in breast cancer progression and autophagy. Cancer and Metastasis Reviews. 2019; 38: 493–506.

[17] Lu X, Kang Y. Organotropism of breast cancer metastasis. Journal of Mammary Gland Biology and Neoplasia. 2007; 12: 153–162.

[18] Shi R, Zhang C, Wu Y, Wang X, Sun Q, Sun J, et al. CDCA2 promotes lung adenocarcinoma cell proliferation and predicts poor survival in lung adenocarcinoma patients. Oncotarget. 2017; 8: 19768–19779.

[19] Feng Y, Qian W, Zhang Y, Peng W, Li J, Gu Q, et al. CDCA2 promotes the proliferation of colorectal cancer cells by activating the AKT/CCND1 pathway in vitro and in vivo. BMC Cancer. 2019; 19: 576.

[20] Uchida F, Uzawa K, Kasamatsu A, Takatori H, Sakamoto Y, Ogawara K, et al. Overexpression of CDCA2 in human squamous cell carcinoma: correlation with prevention of G1 phase arrest and apoptosis. PLOS ONE. 2013; 8: e56381.

[21] Wu ZH, Fang M, Zhou Y. Comprehensive analysis of the expression and prognosis for CDCAs in head and neck squamous cell carcinoma. PLOS ONE. 2020; 15: e0236678.

[22] Jin W, Zhou A, Chen J, Cen Y. CDCA2 promotes proliferation and migration of melanoma by upregulating CCAD1. European Review for Medical and Pharmacological Sciences. 2020; 24: 6858–6863.

[23] Cho S, Li D, Stafford LJ, Luo J, Rodriguez‐Villanueva M, Wang Y, et al. KiSS1 suppresses TNFα-induced breast cancer cell invasion via an inhibition of RhoA-Mediated NF-κB activation. Journal of Cellular Biochemistry. 2009; 107: 1139–1149.

[24] Ong CP, Lee WL, Tang YQ, Yap WH. Honokiol: a review of its anticancer potential and mechanisms. Cancers. 2020; 12: 48.

[25] Pupaki D, Bachurska S, Parvanov D, Ankova D, Rashev P. Association between the Expression of KISS1, KISS1R and MMP-9 in invasive breast carcinomas. Proceedings of the Bulgarian Academy of Sciences. 2022; 75: 1514–1521.

[26] Harihar S, Welch DR. KISS1 metastasis suppressor in tumor dormancy: a potential therapeutic target for metastatic cancers? Cancer and Metastasis Reviews. 2023; 42: 183–196.

[27] Singh N, Hutson R, Milton NGN, Javid FA. Ovarian cancer and KiSS-1 gene expression: a consideration of the use of Kisspeptin plus Kisspeptin aptamers in diagnostics and therapy. European Journal of Pharmacology. 2022; 917: 174752.

[28] Song GQ, Zhao Y. Different therapeutic effects of distinct KISS1 fragments on breast cancer in vitro and in vivo. International Journal of Oncology. 2013; 43: 1219–1227.

[29] Singh R, Bhatt ML, Singh SP, Kumar V, Goel MM, Mishra DP, et al. Evaluation of KiSS1 as a prognostic biomarker in North Indian breast cancer cases. Asian Pacific Journal of Cancer Prevention. 2016; 17: 1789–1795.

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