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Regulation of miR-21 expression in human melanoma via UV-ray-induced melanin pigmentation
Kuan-Yu Lin1,2, Chien-Min Chen3,4, Cheng-You Lu2,5
1Department of Nursing, Central Taiwan University of Science and Technology, Taichung, 40601, Taiwan.
Abstract:
Excessive environmental ultraviolet (UV) radiation produces genetic mutations that can lead to skin cancer. This study was designed to assess the potential inhibitory activity of microRNA-21 (miR-21) on the UV irradiation-stimulated melanogenesis signal pathway in melanoma cells. The molecular mechanism of miR-21-induced inhibitory activity on UV-ray-stimulated melanogenesis-regulating proteins was examined in A375.S2 human melanoma and B16F10 mouse melanoma cells. UV irradiation for 30 min induced melanogenesis signal pathway by increasing melanin production and the number of A375.S2 cells. Similarly, UV radiation increased the expression of α-melanocyte-stimulating hormone (α-MSH) protein and decreased the melanogenesis-regulating signal, such as EGFR and Akt phosphorylation. Notably, miR-21 overexpression in UV-ray-stimulated A375.S2 cells decreased α-MSH expression and increased EGFR and Akt phosphorylation levels. Furthermore, miR-21 on UV-ray- induced melanogenesis was down-regulated by the Akt inhibitor and the EGFR inhibitor (Gefitinib). Results suggest that the suppressive activity of miR-21 on UV-ray-stimulated melanogenesis may involve the down-regulation of α-MSH and the activation in both of EGFR and Akt.
Insights
MicroRNA-21 (miR-21) can inhibit UV-induced skin cancer by suppressing melanogenesis signaling. Overexpressing miR-21 in melanoma cells reduced melanin production and modulated key proteins in the UV-stimulated pathway.
Area of Science:
- Molecular biology
- Dermatology
- Cancer research
Background:
- Excessive environmental ultraviolet (UV) radiation is a known mutagen that can initiate skin cancer.
- Melanogenesis, the process of melanin production, is a key factor in skin pigmentation and UV protection, but its dysregulation can contribute to skin cancer development.
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play critical roles in various cellular processes, including cancer.
Purpose of the Study:
- To investigate the inhibitory effect of microRNA-21 (miR-21) on the UV irradiation-stimulated melanogenesis signaling pathway in melanoma cells.
- To elucidate the molecular mechanisms underlying miR-21's action on proteins involved in UV-induced melanogenesis.
- To assess the potential of miR-21 as a therapeutic target for UV-induced skin cancer.
Main Methods:
- Utilized A375.S2 human melanoma and B16F10 mouse melanoma cell lines.
- Exposed cells to UV irradiation and analyzed changes in melanin production and cell proliferation.
- Measured the expression levels of alpha-melanocyte-stimulating hormone (α-MSH) and the phosphorylation status of epidermal growth factor receptor (EGFR) and Akt.
- Overexpressed miR-21 in UV-irradiated cells and assessed its impact on the melanogenesis pathway.
- Investigated the role of Akt and EGFR signaling by using specific inhibitors (e.g., Gefitinib).
Main Results:
- UV irradiation (30 min) stimulated melanogenesis, increasing melanin production and A375.S2 cell numbers.
- UV radiation elevated α-MSH protein expression while decreasing EGFR and Akt phosphorylation.
- Overexpression of miR-21 in UV-exposed cells led to decreased α-MSH and increased EGFR and Akt phosphorylation.
- The suppressive effect of miR-21 on UV-induced melanogenesis was diminished by Akt and EGFR inhibitors.
Conclusions:
- miR-21 exhibits suppressive activity against UV-ray-stimulated melanogenesis in melanoma cells.
- The inhibitory mechanism of miR-21 involves down-regulating α-MSH and activating EGFR and Akt signaling pathways.
- These findings suggest miR-21's potential role in mitigating UV-induced skin damage and cancer progression.