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DIAPH3 is a prognostic biomarker and inhibit colorectal cancer progression through maintaining EGFR degradation

Renli Huang1, Cheng Wu2, Jialing Wen3

  • 1Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Cancer Medicine
|May 11, 2022
PubMed
Abstract

Insights

Actin cytoskeleton genes impact colorectal cancer (CRC) progression. Diaphanous-related formin 3 (DIAPH3) is downregulated in CRC, and its knockdown promotes cancer cell proliferation and migration by affecting EGFR signaling.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Actin cytoskeleton dynamics are crucial for colorectal cancer (CRC) cell proliferation and migration.
  • The specific roles of actin cytoskeleton genes (ACGs) in CRC progression and their potential as therapeutic targets remain largely unexplored.

Purpose of the Study:

  • To investigate the role of hub prognosis-related ACGs, specifically Diaphanous-related formin 3 (DIAPH3), in colorectal cancer (CRC).
  • To evaluate DIAPH3 as a potential novel therapeutic target and prognostic biomarker in CRC.

Main Methods:

  • Utilized the Kyoto Encyclopedia of Genes and Genomes (KEGG) ACGs gene set for patient grouping and Cox regression analysis to identify prognostic ACGs.
  • Assessed DIAPH3 expression in CRC and its functional role using shRNA in CRC cell lines (KM12, SW480).
  • Analyzed epidermal growth factor receptor (EGFR) activation via western blot and immunofluorescence.

Main Results:

  • Actin cytoskeleton function is a significant prognostic factor in CRC, correlating with T stage and lymph node metastasis.
  • A prognostic model based on four ACGs demonstrated moderate 1-year survival prediction (AUC = 0.71).
  • DIAPH3 was found to be downregulated in CRC; its knockdown enhanced CRC cell proliferation and migration, and increased EGFR phosphorylation by inhibiting lysosomal transport.

Conclusions:

  • ACGs are significant in CRC invasion and prognosis prediction.
  • DIAPH3 shows potential as a novel prognostic biomarker for CRC.
  • DIAPH3 may inhibit CRC progression by regulating EGFR degradation.
Keywords:
DIAPH3EGFRactin cytoskeletoncolorectal cancerprognosis

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