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Updated: Oct 22, 2025

Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
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.
Background:
Circular RNAs (circRNAs) are key regulators in the progression of various cancers. Abnormal DNA methylation patterns feature prominently in the regulation of the expression of tumor-related genes. This study is aimed at investigating the molecular mechanism of circ_0040809 affecting colorectal cancer (CRC) progression by regulating DNA methyltransferase 1 (DNMT1).
Methods:
circ_0040809 was selected from the circRNA microarray datasets (GSE142837 and GSE138589). Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to examine the expression of circ_0040809, miR-515-5p, and DNMT1 mRNA in paired cancerous and paracancerous tissues of 40 CRC patients, as well as in cell lines. Western blotting was conducted for detecting DNMT1 protein expression in CRC cells. Cell proliferation, migration, and apoptosis were assessed through CCK-8, Transwell, and flow cytometry assays. Bioinformatics and dual-luciferase gene assay were conducted to predict and verify, respectively, the targeted relationships between circ_0040809 and miR-515-5p, as well as between miR-515-5p and DNMT1 mRNA.
Results:
In CRC tissues and cells, circ_0040809 and DNMT1 expression are markedly increased, whereas miR-515-5p expression is decreased. Also, high circ_0040809 expression is significantly linked to shorter overall survival. Cell function compensation experiments reveal that circ_0040809 silencing inhibits CRC cell proliferation and migration and promotes apoptosis, while circ_0040809 overexpression has the opposite effects. Mechanistically, circ_0040809 competitively binds to miR-515-5p to elevate DNMT1 expression. Rescue assay reveals that overexpressed miR-515-5p partly counteracts the tumor-facilitating impact of circ_0040809.
Conclusions:
circ_0040809 facilitates CRC cell proliferation and migration, and inhibits apoptosis, through modulating miR-515-5p/DNMT1 axis. Our study implies that targeting circ_0040809 may be a therapy strategy for CRC treatment.
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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