The inhibitory effect of silencing CDCA3 on migration and proliferation in bladder urothelial carcinoma

Abstract

Background CDCA3 is an important component of the E3 ligase complex with SKP1 and CUL1, which could regulate the progress of cell mitosis. CDCA3 has been widely identified as a proto-oncogene in multiple human cancers, however, its role in promoting human bladder urothelial carcinoma has not been fully elucidated. Methods Bioinformatic methods were used to analyze the expression level of CDCA3 in human bladder urothelial carcinoma tissues and the relationship between its expression level and key clinical characteristics. In vitro studies were performed to validate the specific functions of CDCA3 in regulating cell proliferation, cell migration and cell cycle process. Alterations of related proteins was investigated by western blot assays. In vivo studies were constructed to validate whether silencing CDCA3 could inhibit the proliferation rate in mice model. Results Bioinformatic analysis revealed that CDCA3 was significantly up-regulated in bladder urothelial carcinoma samples and was related to key clinical characteristics, such as tumor grade and metastasis. Moreover, patients who had higher expression level of CDCA3 tend to show a shorter life span. In vitro studies revealed that silencing CDCA3 could impair the migration ability of tumor cells via down-regulating EMT-related proteins such as MMP9 and Vimentin and inhibit tumor cell growth via arresting cells in the G1 cell cycle phase through regulating cell cycle related proteins like p21. In vivo study confirmed that silencing CDCA3 could inhibit the proliferation of bladder urothelial carcinoma cells. Conclusions CDCA3 is an important oncogene that could strengthen the migration ability of bladder urothelial carcinoma cells and accelerate tumor cell growth via regulating cell cycle progress and is a potential biomarker of bladder urothelial carcinoma.

Cell Division Cycle-Associated Protein 3 (CDCA3) Is a Potential Biomarker for Clinical Prognosis and Immunotherapy in Pan-Cancer

“…More and more studies have confirmed that dysregulated expression of CDCA3 plays a vital role in cancer progression. The clinical treatment effect of cancer patients with high expression of CDCA3 is worse, and CDCA3 may become a new potential prognostic marker and a new therapeutic target for cancer [42][43][44][45].…”

Identification of candidate biomarkers correlated with poor prognosis of breast cancer based on bioinformatics analysis

“…These three genes were consistent with predicted results. CDCA3 is a FBOX protein, and is essential for cell mitosis [ 78 ], which take part in forming E3 ligase complex and relate to ubiquitination. It triggers cells to enter mitosis and dephosphorylation of CDC2 proteins in G2 phase.…”

Long noncoding RNA ST8SIA6‐AS1 promotes cell proliferation and metastasis in triple‐negative breast cancer by targeting miR‐145‐5p/CDCA3 to inactivate the p53/p21 signaling pathway

“…Consistent with our finding, a previous report demonstrated that ST8SIA6-AS1 promoted cholangiocarcinoma progression by inhibiting miR-145-5p to up-regulate MAL2 expression. 18 CDCA3 (cell division cycle associated protein 3), also known as a trigger of mitosis entry 1 (TOME-1), is reported to be up-regulated and exert oncogenic properties in different human tumors, such as nonsmall cell lung cancer, 33 bladder urothelial carcinoma, 34 colorectal cancer, 35 and oral cancer. 36 What's more, CDCA3 was highly expressed in clinical tumor samples of breast cancer, and high CDCA3 expression was associated with a poor prognosis.…”