CDCA2 promotes the proliferation of colorectal cancer cells by activating the AKT/CCND1 pathway in vitro and in vivo

Abstract

Background Cell division cycle associated 2 (CDCA2), upregulated in lung adenocarcinoma and oral squamous cell carcinoma, may be related to some malignant diseases. Nevertheless, its role in colorectal cancer (CRC) remains unknown. Methods CDCA2 expression was analyzed using The Cancer Genome Atlas (TCGA), quantitative real-time PCR (qRT-PCR), and immunohistochemistry. The impact of CDCA2 on cell proliferation was analyzed via loss- or gain-of-function assays. Furthermore, gene set enrichment analysis was conducted to explore the potential mechanism of CDCA2 in CRC. Lastly, the expression levels of CCND1 and AKT were measured in CRC cell lines. Results Our study revealed that CDCA2 expression was associated with tumor progression. Through loss- or gain-of-function assays, we found that upregulation of CDCA2 promoted the proliferation of DLD-1 cells, however, downregulation of CDCA2 in SW480 cells restrained proliferative capacity both in vitro and in vivo . The results of flow cytometry showed that CDCA2 promoted cell cycle progression via upregulation of CCND1 in CRC cell lines. In the following experiments, we found that CDCA2 regulated CCND1 expression through activating the PI3K/AKT pathway, and confirmed this using a specific PI3K inhibitor (LY294002). Conclusions This study demonstrates that overexpression of CDCA2 might target CCND1 to promote CRC cell proliferation and tumorigenesis through activation of the PI3K/AKT pathway.

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

“…Recent research results demonstrate that CDCA2 methylation in HeLa cells promotes cell proliferation and suppresses apoptosis [26]. Additionally, CDCA2 overexpression promotes the proliferation of CRC cells and oral squamous cell carcinoma (OSCC) cells [27,28]. Furthermore, a study on lung adenocarcinoma suggests that CDCA2 proliferates lung adenocarcinoma cells and predicts the poor prognosis for these patients [29].…”

Increased Expression of CDCA2 in Glioma Predicts Poor Prognosis as Identified by Population-based Analysis

“…It is necessary for us to explore more prognostic markers to further understand the mechanism of glioma and predict prognosis of patients with glioma. The researches of cancer development revealed that CDCA2 was related to the occurrence and development in multiple cancers [11,12,21,22]. To our knowledge, the expression of CDCA2 and its potential prognostic impact on glioma has not been explored.…”

“…CDCA2 was also over-expressed in other cancer types and associated with poor prognosis. Recent study demonstrated that CDCA2 promoted colorectal cancer cells proliferation by activating the AKT/CCND1 pathway in vitro and in vivo [11]. More studies were carried out to identify that CDCA could be an signature gene with prognostic value for luminal breast cancer, esophageal squamous cell carcinoma, bladder cancer, melanoma and Synovial sarcoma [12,13,21,23].…”

A Nuclear Stress Pathway that Parallels Cytoplasmic Stress Granule Formation

“…As a consequence, excess RepoMan desensitizes cells to DNA damage ( Peng et al., 2010 ), which can decrease genomic stability by allowing mutations to accumulate. Consistent with a pro-survival role, overexpression of RepoMan promotes proliferation of colorectal cancer and lung cancer adenocarcinoma cells in culture ( Feng et al., 2019 ; Shi et al., 2017 ) while knockdown sensitizes oral squamous cell carcinoma cells to DNA damage-induced apoptosis ( Uchida et al., 2013 ).…”

“…Increasing evidence points to RepoMan as a strong prognostic indicator that is elevated in numerous human cancers. RepoMan mRNA transcripts are overexpressed in late-stage cancers, with increased levels observed in breast, ovary, lung, and colon cancer tissues ( Feng et al., 2019 ; Peng et al., 2010 ; Shi et al., 2017 ), as well as in oral squamous cell carcinoma and malignant breast cancer cell lines ( Peng et al., 2010 ; Uchida et al., 2013 ; Vagnarelli, 2014 ). It is part of a cohort of 18 signature genes associated with malignant melanoma progression ( Ryu et al., 2007 ) and one of two top-ranked genes correlated with metastatic behavior of synovial sarcomas ( Lagarde et al., 2013 ).…”