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miR-617 Promotes the Growth of IL-22-Stimulated Keratinocytes Through Regulating FOXO4 Expression
Tao Liu1, Xiaomei Feng2, Yongmei Liao3
1Department of Dermatology, The Affiliated Hospital of Southwest Medical University, No. 25 of Taiping Road, Luzhou, 646000, Sichuan, China. TaoLiufjk@163.com.
Abstract:
Psoriasis is considered as a common chronic and relapsing inflammatory skin disease. MicroRNAs (miRNAs) were found to be related with psoriasis pathogenesis. Nevertheless, the function of miR-617 in psoriasis is still unclear. The miR-617 RNA level was detected using quantitative reverse transcription-PCR (qRT-PCR). Western blot analysis examined the protein level. Cell proliferation was analyzed via cell counting kit-8 (CCK-8) assay. Flow cytometry analysis detected cell cycle and apoptosis. The relationship between miR-617 and forkhead box protein O4 (FOXO4) was confirmed through dual luciferase assay. The miR-617 was up-regulated in psoriatic skin tissues and interleukin-22 (IL-22)-stimulated immortalized human keratinocyte HaCaT cells. Moreover, miR-617 mimics promoted proliferation, cell cycle, and suppressed apoptosis in IL-22-stimulated HaCaT cells. However, miR-617 inhibitor showed opposite effects. Additionally, FOXO4 was a target of miR-617. FOXO4 was down-regulated in psoriatic skin tissues and IL-22-stimulated HaCaT cells. Negative correlation between miR-617 and FOXO4 was identified. FOXO4 overexpression alleviated the effects of miR-617 proliferation, cell cycle and apoptosis in the IL-22-stimulated HaCaT cells. These results demonstrate that miR-617 increases the growth of IL-22-stimulated keratinocytes through targeting FOXO4, which provides a new therapeutic target for psoriasis.
Insights
MicroRNA-617 (miR-617) promotes psoriasis by increasing keratinocyte proliferation via targeting FOXO4. Inhibiting miR-617 may offer a new therapeutic strategy for this chronic inflammatory skin disease.
Area of Science:
- Dermatology
- Molecular Biology
- Genetics
Background:
- Psoriasis is a chronic inflammatory skin condition with complex pathogenesis.
- MicroRNAs (miRNAs) play a role in psoriasis development, but miR-617's specific function remains elusive.
Purpose of the Study:
- To investigate the role of miR-617 in psoriasis pathogenesis.
- To identify the molecular targets and mechanisms of miR-617 in keratinocytes.
Main Methods:
- Quantitative reverse transcription-PCR (qRT-PCR) and Western blot to measure miR-617 and FOXO4 levels.
- Cell counting kit-8 (CCK-8) assay for proliferation, flow cytometry for cell cycle and apoptosis.
- Dual luciferase assay to confirm the targeting relationship between miR-617 and FOXO4.
Main Results:
- miR-617 was upregulated in psoriatic tissues and IL-22-stimulated keratinocytes.
- miR-617 mimics enhanced proliferation and cell cycle, while suppressing apoptosis; inhibitors had opposite effects.
- FOXO4 was identified as a direct target of miR-617 and was downregulated in psoriasis; FOXO4 overexpression counteracted miR-617's effects.
Conclusions:
- miR-617 promotes keratinocyte proliferation in IL-22-stimulated cells by targeting FOXO4.
- This miR-617/FOXO4 axis represents a potential therapeutic target for psoriasis treatment.
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