Friday, June 14, 2019

CDCA2 promotes the proliferation of colorectal cancer cells by activating the AKT/CCND1 pathway in vitro and in vivo | BMC Cancer | Full Text

CDCA2 promotes the proliferation of colorectal cancer cells by activating the AKT/CCND1 pathway in vitro and in vivo | BMC Cancer | Full Text

BMC Cancer

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

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Contributed equally
BMC Cancer201919:576
  • Received: 18 July 2018
  • Accepted: 5 June 2019
  • Published: 
Open Peer Review reports

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.

Keywords

  • CDCA2
  • CCND1
  • Proliferation
  • PI3K/AKT pathway
  • Colorectal cancer

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