Downregulation of DEAD-box helicase 21 (DDX21) inhibits proliferation, cell cycle, and tumor growth in colorectal cancer via targeting cell division cycle 5-like (CDC5L)

Bioengineered. 2021 Dec;12(2):12647-12658. doi: 10.1080/21655979.2021.2011636.

Abstract

Identification of novel anti-tumor target is crucial for cancer diagnosis, prognosis, and therapeutic strategy. The study aimed to explore the roles and interaction of DEAD-box helicase 21 (DDX21) and cell division cycle 5-like (CDC5L) in colorectal cancer (CRC) progression. Levels of DDX21 and CDC5L were detected in colorectal cancer cell lines by RT-qPCR and Western blot assay. The role of DDX21 and CDC5L on the cell proliferation, cell cycle and tumor growth were evaluated both in vitro and in vivo. The interaction of DDX21 and CDC5L was predicted by The STRING publicly available data and verified by immunoprecipitation. The results showed that DDX21 was dramatically upregulated in colorectal cancer cells. In vivo and in vitro experiments revealed that downregulation of DDX21 suppressed colorectal cancer cell proliferation, colony formation, cell cycle development, and tumor growth, while overexpression of CDC5L reversed the suppressive effects of DDX21 silencing. Furthermore, DDX21 interacted with CDC5L to exert the tumor-promoting effects in CRC. In summary, the data indicate a novel role for DDX21/CDC5L in the development of CRC, which enrich the therapeutic strategy for CRC.

Keywords: CDC5L; DDX21; cell cycle arrest; colorectal cancer; proliferation.

MeSH terms

  • Animals
  • Cell Cycle / genetics*
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • DEAD-box RNA Helicases / genetics*
  • DEAD-box RNA Helicases / metabolism
  • Disease Progression
  • Down-Regulation / genetics*
  • Female
  • G2 Phase / genetics
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mitosis / genetics
  • Protein Binding
  • RNA-Binding Proteins / metabolism*

Substances

  • CDC5L protein, human
  • Cell Cycle Proteins
  • RNA-Binding Proteins
  • DDX21 protein, human
  • DEAD-box RNA Helicases

Grants and funding

The author(s) reported there is no funding associated with the work featured in this article.