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Updated: Dec 23, 2025

Isolation, Culture, and Characterization of Primary Dermal Fibroblasts from Human Keloid Tissue
Published on: July 28, 2023
miR-4417 suppresses keloid fibrosis growth by inhibiting CyclinD1
1Department of Plastic Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Abstract:
Mounting evidence has reported that microRNAs (miRNAs) play irreplaceable roles in the development of keloid fibrosis. miR-4417 has been reported to contribute to nickel chloride-promoted lung epithelial cell fibrogenesis and tumorigenesis. However, whether miR-4417 is involved in keloid fibrogenesis as well as its underlying mechanisms remain largely elusive. In this study, the expression levels of miR-4417 and CyclinD1 in keloid tissues and fibroblasts were examined by qRT-PCR. Cell proliferation was determined by CCK assay. Western blot and flow cytometry were performed to evaluate cell apoptosis. Cell migration and invasion were measured by Transwell assay. Luciferase reporter assay was used to confirm the relationship between miR4417 and CyclinD1. As a result, we found that miR-4417 was significantly down-regulated in keloid tissues and fibroblasts. miR-4417 up-regulation led to the suppression of proliferation, migration, and invasion, while induced cell apoptosis in keloid fibroblasts. However, miR-4417 depletion exerted an opposite effect. CyclinD1 harbored the binding sites with miR-4417. Besides, the expression of CyclinD1 was evidently decreased in keloid tissues and fibroblasts. Meanwhile, miR-4417 was negatively correlated with CyclinD1 in keloid tissue. The effect of CyclinD1 knockdown on keloid fibroblasts was similar to that of miR-4417 overexpression. Furthermore, the elevated of CyclinD1 expression rescued the effect of miR-4417 up-regulation on keloid fibroblasts. miR-4417/CyclinD1 axis was required for cell proliferation, apoptosis, migration, and invasion in keloid fibroblasts. In conclusion, miR-4417 and CyclinD1 may be potential therapeutic targets for the treatment of keloid.
Insights
MicroRNA-4417 (miR-4417) is down-regulated in keloid fibrosis, suppressing cell proliferation and migration. Restoring miR-4417 levels may offer a new therapeutic strategy for keloid treatment.
Area of Science:
- Biomedical research
- Molecular biology
- Dermatology
Background:
- MicroRNAs (miRNAs) are crucial in keloid fibrosis development.
- The specific role of miR-4417 in keloid fibrogenesis is largely unknown.
- Previous studies linked miR-4417 to fibrogenesis in lung epithelial cells.
Purpose of the Study:
- To investigate the role of miR-4417 in keloid fibrogenesis.
- To elucidate the underlying molecular mechanisms involving miR-4417 and CyclinD1.
- To assess the therapeutic potential of targeting the miR-4417/CyclinD1 axis in keloids.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) for miR-4417 and CyclinD1 expression.
- Cell Counting Kit (CCK) assay for cell proliferation.
- Western blot and flow cytometry for cell apoptosis.
- Transwell assays for cell migration and invasion.
- Luciferase reporter assay to confirm miR-4417 and CyclinD1 interaction.
Main Results:
- miR-4417 was significantly downregulated in keloid tissues and fibroblasts.
- Overexpression of miR-4417 inhibited keloid fibroblast proliferation, migration, and invasion, while promoting apoptosis.
- CyclinD1 expression was decreased in keloids and directly targeted by miR-4417.
- miR-4417 negatively correlated with CyclinD1 expression in keloid tissues.
- Modulating CyclinD1 mimicked or reversed the effects of miR-4417, confirming the miR-4417/CyclinD1 axis's role.
Conclusions:
- miR-4417 acts as a tumor suppressor in keloid fibroblasts by inhibiting proliferation, migration, and invasion, and inducing apoptosis.
- The miR-4417/CyclinD1 axis is a critical regulator of keloid fibroblast behavior.
- miR-4417 and CyclinD1 represent potential therapeutic targets for keloid treatment.
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