Suppression of CDCA3 inhibits prostate cancer progression via NF‑κB/cyclin D1 signaling inactivation and p21 accumulation

Abstract

Dysregulation of the cell cycle contributes to tumor progression. Cell division cycle-associated 3 (CDCA3) is a known trigger of mitotic entry and has been demonstrated to be constitutively upregulated in tumors. It is therefore associated with carcinogenic properties reported in various cancers. However, the role of CDCA3 in prostate cancer is unclear. In the present study, western blotting and analysis of gene expression profiling datasets determined that CDCA3 expression was upregulated in prostate cancer and was associated with a poor prognosis. CDCA3 knockdown in DU145 and PC-3 cells led to decreased cell proliferation and increased apoptosis, with increased protein expression levels of cleaved-caspase3. Further experiments demonstrated that downregulated CDCA3 expression levels induced G0/G1 phase arrest, which was attributed to increased p21 protein expression levels and decreased cyclin D1 expression levels via the regulation of NF-κB signaling proteins (NFκB-p105/p50, IKKα/β, and pho-NFκB-p65). In conclusion, these results indicated that CDCA3 may serve a crucial role in prostate cancer and consequently, CDCA3 knockdown may be used as a potential therapeutic target.

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

“…47 Knockdown of CDCA3 inhibited prostate cancer progression by accumulating p21 and inhibiting cyclin D1 through inactivating the NF-κB signaling pathway. 48 Here, we further confirmed that CDCA3 inhibited p53 and p21 expression in TNBC cells, indicating the inactivation of CDCA3 on p53/p21 signaling. However, depletion of CDCA3 triggered an increase in p21 independent of p53 in NSCLC cells.…”

“…CDCA3 was also demonstrated to promote cell proliferation and tumorigenesis in colorectal cancer by repressing p21 expression 47 . Knockdown of CDCA3 inhibited prostate cancer progression by accumulating p21 and inhibiting cyclin D1 through inactivating the NF‐κB signaling pathway 48 . Here, we further confirmed that CDCA3 inhibited p53 and p21 expression in TNBC cells, indicating the inactivation of CDCA3 on p53/p21 signaling.…”

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].…”

Pan-cancer analysis identifies CDCA3 as a novel prognostic marker associated with immune infiltration in lung adenocarcinoma through bioinformatics analysis

“…However, controversial outcomes still exist; for example, knockdown of CDCA3 in NCSLC reduces the proliferation of NCSLC cells by stagnating them in G2/ M phase (23). In colorectal cancer (CRC) and PC, CDCA3 induces cell cycle arrest in the G1 phase (24,25). In addition, CDCA3 also affects the progression of GC through epigenetics.…”

“…KEGG pathway analysis indicated that CDCA3 was involved in cell cycle, proteasome, spliceosome, and DNA replication pathways. Studies have shown that CDCA3 activates the nuclear factor kappa B (NF-KB)/cyclin D1 signaling pathway and promotes cancer cell proliferation in CRC and PC (25). In breast cancer and pancreatic cancer, CDCA3 plays a critical role in tumor progression through activation of the phosphoinositide 3-kinases (PI3K)/AKT pathway (7,32).…”