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Small protein DDX11-AS1-ORF encoded by lncRNA DDX11-AS1 promotes colorectal cancer progression through

Yuanfang Cheng1, Jiajie Dong1, Kai Shang2

  • 1Department of Biochemistry and Molecular Biology, Sanquan College of Xinxiang Medical University, School of Basic Medicine Xinxiang 453513, Henan, P. R. China.

American Journal of Cancer Research
|May 15, 2025
PubMed

Insights

The small protein DDX11-AS1-ORF, encoded by DDX11-AS1, promotes colorectal cancer (CRC) progression. It enhances tumor proliferation, migration, and angiogenesis by activating the VEGFA/p38-MAPK pathway, offering a potential therapeutic target.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cancer Research

Background:

  • Colorectal cancer (CRC) progression involves complex molecular mechanisms.
  • Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer.
  • The functional role of small proteins encoded by lncRNAs in CRC remains underexplored.

Purpose of the Study:

  • To investigate the expression, function, and mechanism of the small protein DDX11-AS1-ORF in colorectal cancer (CRC).
  • To elucidate the role of DDX11-AS1 and its encoded protein in CRC progression.
  • To identify potential therapeutic targets for CRC.

Main Methods:

  • Quantitative reverse transcription polymerase chain reaction (qRT-PCR) for gene expression analysis.
  • Cell counting kit-8 (CCK8), colony formation, Transwell migration, and in vitro tube formation assays for functional evaluation.
  • Western blot and immunofluorescence for protein validation and pathway analysis.
  • Inhibition of the p38-MAPK pathway using SB203580.

Main Results:

  • DDX11-AS1 was significantly upregulated in CRC tissues and cells.
  • DDX11-AS1 translated into a functional small protein, DDX11-AS1-ORF, promoting CRC cell proliferation, migration, and angiogenesis.
  • DDX11-AS1-ORF activated the p38-MAPK signaling pathway via VEGFA, driving tumor progression.
  • Inhibition of p38-MAPK pathway suppressed DDX11-AS1-ORF-mediated tumor promotion.

Conclusions:

  • The small protein DDX11-AS1-ORF, derived from DDX11-AS1, is a key driver of colorectal cancer.
  • DDX11-AS1-ORF promotes CRC by enhancing proliferation, migration, and angiogenesis through the VEGFA/p38-MAPK pathway.
  • DDX11-AS1-ORF represents a novel and promising molecular target for CRC therapy.
Keywords:
Colorectal cancerVEGFAlncRNAp38-MAPK pathwaysmall protein

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