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G-quadruplex-enhanced circular single-stranded DNA (G4-CSSD) adsorption of miRNA to inhibit colon cancer progression

Haidong Wu1, Weilong Zhong2, Ronghua Zhang3

  • 1Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs and Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.

Cancer Medicine
|March 1, 2023
PubMed
Abstract

Insights

This study introduces G4-CSSD, a novel DNA structure that restores tumor suppressor genes to inhibit colon cancer progression. By targeting miR-590-3p, it upregulates key genes, reducing cancer cell proliferation and metastasis.

Area of Science:

  • Genomics and Molecular Biology
  • Cancer Research
  • Biotechnology

Background:

  • Tumorigenesis is driven by chromosomal heterogeneity, affecting oncogene and tumor suppressor gene expression.
  • Targeted therapies for oncogenes are established, but developing drugs for randomly mutated tumor suppressor genes remains challenging.
  • Early research demonstrated artificial circular single-stranded DNA (CSSD) can restore tumor suppressor gene function by adsorbing microRNA (miRNA).

Purpose of the Study:

  • To develop an improved CSSD, termed G4-CSSD, with enhanced stability and efficacy for cancer therapy.
  • To investigate the potential of G4-CSSD in restoring tumor suppressor gene function and inhibiting colon cancer progression.
  • To identify and validate key tumor suppressor genes and their regulatory miRNAs in colon cancer.

Main Methods:

  • G4-CSSD was designed as a fully closed single-stranded DNA incorporating a G quadruplex secondary structure.
  • The Cancer Genome Atlas (TCGA) and Human Protein Atlas databases were utilized to identify potential tumor suppressor genes in colon cancer.
  • In vitro and in vivo experiments were conducted to assess the efficacy of G4-CSSD in colon cancer models.

Main Results:

  • Simultaneous low expression of CLCA1, B3GNT6, and UGT2A3 was correlated with favorable prognosis in colon cancer.
  • G4-CSSD590 effectively repressed miR-590-3p, leading to the upregulation of CLCA1, B3GNT6, and UGT2A3.
  • The restoration of these tumor suppressor genes significantly inhibited colon cancer cell proliferation and metastasis.

Conclusions:

  • G4-CSSD represents a promising therapeutic strategy for colon cancer by restoring tumor suppressor gene function.
  • This approach offers a novel avenue for developing targeted treatments for cancers with compromised tumor suppressor genes.
  • Further research into G4-CSSD could lead to new clinical interventions for colon cancer patients.
Keywords:
G quadruplexcircular single-stranded DNAcolon cancermicroRNA inhibitortumour suppressor gene

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