Hsa_circ_0040809 regulates colorectal cancer development by upregulating methyltransferase DNMT1 via targeting

Guoliang Mao1, Bing Zhou1, Wuqin Xu1

  • 1Department of Pathology, First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu, Anhui, China.

Abstract

Insights

Circular RNA circ_0040809 promotes colorectal cancer (CRC) by increasing DNA methyltransferase 1 (DNMT1) via sponging miR-515-5p. Targeting circ_0040809 offers a potential therapeutic strategy for CRC.

Area of Science:

  • Molecular Biology
  • Oncology
  • Epigenetics

Background:

  • Circular RNAs (circRNAs) are crucial in cancer progression.
  • Aberrant DNA methylation patterns regulate tumor-associated genes.
  • This study investigates circ_0040809's role in colorectal cancer (CRC) via DNA methyltransferase 1 (DNMT1).

Purpose of the Study:

  • To elucidate the molecular mechanism of circ_0040809 in colorectal cancer (CRC) progression.
  • To investigate the regulatory relationship between circ_0040809, miR-515-5p, and DNMT1 in CRC.
  • To explore the potential of circ_0040809 as a therapeutic target for CRC.

Main Methods:

  • circRNA expression analysis using microarray datasets (GSE142837, GSE138589).
  • Quantitative real-time PCR (qRT-PCR) and Western blotting to assess gene and protein expression.
  • Functional assays (CCK-8, Transwell, flow cytometry) to evaluate cell proliferation, migration, and apoptosis.
  • Bioinformatics and dual-luciferase assays to confirm molecular interactions.

Main Results:

  • circ_0040809 and DNMT1 expression are upregulated, while miR-515-5p is downregulated in CRC tissues and cells.
  • High circ_0040809 expression correlates with poorer patient survival.
  • circ_0040809 promotes CRC cell proliferation and migration while inhibiting apoptosis by sponging miR-515-5p to upregulate DNMT1.

Conclusions:

  • circ_0040809 drives CRC progression by modulating the miR-515-5p/DNMT1 axis.
  • Targeting circ_0040809 presents a promising therapeutic avenue for colorectal cancer.
  • Understanding the circ_0040809/miR-515-5p/DNMT1 pathway is critical for CRC treatment strategies.

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