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Updated: Mar 31, 2026
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
miR-124 and miR-506 inhibit colorectal cancer progression by targeting DNMT3B and DNMT1
Zhiheng Chen1, Shaojun Liu2, Li Tian2
1Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Abstract:
miR-124 and miR-506 are reportedly down-regulated and associated with tumor progression in many cancers, but little is known about their intrinsic regulatory mechanisms in colorectal cancer (CRC). In this study, we found that the miR-124 and miR-506 levels were significantly lower in human CRC tissues than in controls, as indicated by qRT-PCR and in situ hybridization histochemistry. We also found that the overexpression of miR-124 or miR-506 inhibited tumor cell progression and increased sensitivity to chemotherapy in vitro. Increased miR-124 or miR-506 expression also inhibited tumor cell proliferation and invasion in vivo. Luciferase reporter assays and western blotting were used to determine the association between miR-124, miR-506 and their target genes, DNMTs. We further identified that miR-124 and miR-506 directly targeted DNMT3B and indirectly targeted DNMT1. The overexpression of miR-124 and miR-506 reduced global DNA methylation and restored the expression of E-cadherin, MGMT and P16. In conclusion, our data showed that miR-124 and miR-506 inhibit progression and increase sensitivity to chemotherapy by targeting DNMT3B and DNMT1 in CRC. These findings may provide novel avenues for the development of targeted therapies.
Insights
MicroRNAs miR-124 and miR-506 are lower in colorectal cancer (CRC) and inhibit tumor progression. Restoring their levels sensitizes CRC cells to chemotherapy by targeting DNA methyltransferases.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- MicroRNAs (miRNAs) play crucial roles in cancer development.
- miR-124 and miR-506 are implicated in tumor progression but their role in colorectal cancer (CRC) is unclear.
- Understanding miRNA regulation is vital for developing novel CRC therapies.
Purpose of the Study:
- To investigate the role and regulatory mechanisms of miR-124 and miR-506 in colorectal cancer (CRC).
- To determine if miR-124 and miR-506 can be therapeutic targets for CRC treatment.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) and in situ hybridization to assess miRNA levels in CRC tissues.
- In vitro and in vivo experiments to evaluate the effects of miR-124/miR-506 overexpression on tumor progression.
- Luciferase reporter assays and western blotting to identify miRNA targets.
- DNA methylation analysis.
Main Results:
- miR-124 and miR-506 levels were significantly reduced in human CRC tissues compared to controls.
- Overexpression of miR-124 or miR-506 inhibited CRC cell proliferation, invasion, and enhanced chemotherapy sensitivity in vitro and in vivo.
- miR-124 and miR-506 were identified as direct and indirect regulators of DNA methyltransferases (DNMTs), specifically targeting DNMT3B and DNMT1.
- Restored miR-124/miR-506 expression reduced global DNA methylation and reactivated tumor suppressor genes (E-cadherin, MGMT, P16).
Conclusions:
- miR-124 and miR-506 act as tumor suppressors in colorectal cancer (CRC).
- These miRNAs inhibit CRC progression and chemosensitivity by targeting DNMT3B and DNMT1, leading to reduced DNA methylation.
- miR-124 and miR-506 represent promising therapeutic targets for colorectal cancer treatment.
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