CDCA3 mediates p21-dependent proliferation by regulating E2F1 expression in colorectal cancer

Abstract

Dysregulated cell cycle progression serves a crucial role in tumor development. Cell division cycle- associated 3 (CDCA3) is considered a trigger of mitotic entry; it is an important part of the S phase kinase-associated protein 1/Cullin/F-box ubiquitin ligase complex and mediates the destruction of mitosis-inhibitory kinase wee1. However, little is known about the role of CDCA3 in cancer, particularly colorectal cancer (CRC). The present study aimed to explore the biological and clinical significance of CDCA3 in CRC growth and progression. CDCA3 expression was significantly associated with tumor progression and poor survival. Overexpression of CDCA3 increased proliferation in LoVo CRC cells, whereas CDCA3 knockdown in SW480 CRC cells led to decreased proliferation, in vitro and in vivo. Further mechanistic investigations demonstrated that reduced CDCA3 expression resulted in G1/S phase transition arrest, which was attributed to a significant accumulation of p21 in SW480 cells; conversely, increased CDCA3 expression promoted G1/S phase transition through decreased p21 accumulation in LoVo cells. It was also demonstrated that CDCA3 was able to regulate the expression of transcription factor E2F1, thereby repressing p21 expression. Taken together, these results suggested that overexpression of CDCA3 may serve a crucial role in tumor malignant potential and that CDCA3 may be used as a prognostic factor and a potential therapeutic target in CRC.

The diagnostic and prognostic value of cell division cycle associated gene family in Hepatocellular Carcinoma

“…Some bioinformatics analysis had suggested that CDCA3 contributed to the pathological process in several cancers, including breast cancer [25], bladder cancer [23] and liver cancer [26,27]. Previous studies had shown that the functional loss of CDCA3 might block the transition from the GO/G1 phase of BGC823, H1 and Sa3 cells [2,[7][8][9]. Three retrospectively cohort studies had indicated that CDCA5 was overexpressed in HCC [28][29][30].…”

“…Recently some researchers revealed that CDCAs might contribute to the cancer progression. Previous studies had shown that some members of this gene family might be up-regulated in breast cancer, lung adenocarcinoma and pancreatic adenocarcinoma [5][6][7][8][9][10][11][12][13][14][15][16]. And high expression levels of these genes were identified as poorly predictive factors of survival in these cancers [17,18].…”

Analysis of the Expression of Cell Division Cycle-Associated Genes and Its Prognostic Significance in Human Lung Carcinoma: A Review of the Literature Databases

“…CDCA3 controls the G1 phase [30], which acts as one of the prognostic genes for hepatocellular carcinoma (HCC) [31] and is also involved in LC cell proliferation, migration, invasion, and apoptosis [30], as well as CRC cell proliferation [32]. Moreover, it has been reported that CDCA3 expression is related to prognosis for bladder cancer cases [33] and luminal A breast cancer [34].…”

Identification of grade-specific diagnostic and prognostic biomarkers of key candidate genes and pathways in breast cancer by integrated bioinformatics analysis

“…Previous data analysis indicated that CDCA3 showed on average > 100 -fold overexpression in BC compared with normal tissue 34 . Meantime, CDCA3 has been demonstrated to be expressed in liver cancer, oral squamous cell carcinoma tissue, non-small cell lung cancer and prostate cancer cells 35 . However, the role of CDCA3 in malignant tumors remains unclear.…”