miR-526b targets 3' UTR of MMP1 mRNA
Kyu-Han Kim1, Ji-Yong Jung1, Eui Dong Son1
1Bioscience Research Institute, AmorePacific Corporation R&D Center, Gyeonggi-do, Republic of Korea.
Abstract:
Regulation of matrix metalloproteinases (MMPs) is important for many physiological processes involving cancers, inflammation, tissue remodeling and skin aging. Here, we report the novel finding that the expression of MMP1 mRNA is downregulated by the overexpression of miR-526b which is a member of chromosome 19 microRNA cluster (C19MC). Our analysis using reporter constructs containing the 3' untranslated region (3' UTR) of MMP1 and its mutant form showed that the region from 377-383 in the 3' UTR of MMP1 is critical for targeting by miR-526b. In addition, the expression pattern of miR-526b and MMP1 mRNA showed reverse relation between adult dermal and neonatal fibroblasts. We show for the first time that miR-526b, an miRNA belonging to C19MC, can target the 377-383 region of the MMP1 3' UTR.
Insights
MicroRNA-526b (miR-526b) from the C19MC cluster downregulates matrix metalloproteinase-1 (MMP1) expression. This discovery identifies a specific targeting region in MMP1
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) are crucial for physiological processes, including cancer, inflammation, tissue remodeling, and skin aging.
- Dysregulation of MMPs is implicated in various pathological conditions.
Purpose of the Study:
- To investigate the regulatory role of microRNA-526b (miR-526b) in the expression of matrix metalloproteinase-1 (MMP1).
- To identify the specific targeting mechanism of miR-526b on MMP1 mRNA.
Main Methods:
- Reporter construct assays using wild-type and mutant 3' untranslated regions (3' UTR) of MMP1.
- Analysis of miR-526b and MMP1 mRNA expression patterns in neonatal and adult dermal fibroblasts.
Main Results:
- Overexpression of miR-526b led to the downregulation of MMP1 mRNA expression.
- A specific region (377-383) in the MMP1 3' UTR was identified as critical for miR-526b targeting.
- An inverse relationship between miR-526b and MMP1 mRNA levels was observed in different fibroblast types.
Conclusions:
- MicroRNA-526b, a member of the chromosome 19 microRNA cluster (C19MC), directly targets and downregulates MMP1 expression.
- The 377-383 region of the MMP1 3' UTR is essential for miR-526b-mediated repression.
- This finding provides novel insights into the post-transcriptional regulation of MMP1 by miR-526b.
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