N6-methyladenosine-modified long non-coding RNA AGAP2-AS1 promotes psoriasis pathogenesis via miR-424–5p/AKT3 axis. Issue 1 (January 2022)

• Record Type: Journal Article
• Authors: Xian, Jiayi; Shang, Mingwei; Dai, Yu; Wang, Qi; Long, Xinxin; Li, Jiazheng; Cai, Yantao; Xia, Chenglai; Peng, Xuebiao
• Is Part Of: Journal of dermatological science. Volume 105:Issue 1(2022)
• Page Start: 27
• Page End: 36
• Publication Date: 2022-01
• Subjects: AGAP2-AS1 -- Psoriasis -- M6A -- MiR-424–5p -- AKT3; Dermatology -- Periodicals; Skin Diseases -- Periodicals; Dermatologie -- Périodiques; 616.5005
• DOI: 10.1016/j.jdermsci.2021.11.007
• Languages: English
• ISSNs: 0923-1811

Abstract

Highlights: AGAP2-AS1 levels in psoriatic skin were higher than those in healthy controls. AGAP2-AS1 expression was increased via an m 6 A-YTHDF2-dependent manner. AGAP2-AS1 promotes keratinocyte proliferation through miR-424–5p/AKT3 axis. Abstract: Background: Psoriasis is a chronic, complicated, and recurrent inflammatory skin disease. However, the precise molecular mechanisms remain largely elusive and the present treatment is unsatisfactory. Objective: This study aimed to unravel the functions of long noncoding RNA (lncRNA) AGAP2-AS1 and its biological mechanism in psoriasis pathogenesis, hinting for the new therapeutic targets in psoriasis. Methods: The expression of AGAP2-AS1 in the skin tissue of psoriasis patients and healthy controls were detected by qRT-PCR and RNAscope®. Cell Counting Kit‑8 (CCK8) and clone formation assays were utilized to assess proliferation. Methylated RNA immunoprecipitation (MeRIP) was performed to detect the N 6 -methyladenosine (m 6 A) modification. RNA immunoprecipitation (RIP) was used to detect the interaction of AGAP2-AS1 with YTH domain family 2(YTHDF2). The relationships among AGAP2-AS1, miR-424–5p and AKT3 were examined by dual-luciferase reporter assay and RIP assay. Results: We found that AGAP2-AS1 level was upregulated in the skin tissue of psoriasis patients than that of healthy controls and AGAP2-AS1 could promote proliferation and inhibit apoptosis of keratinocytes. Methyltransferase like 3(METTL3)-mediated m6A modification suppressed the expression of AGAP2-AS1 via YTHDF2-dependent AGAP2-AS1 stability. Thus, downregulation of METTL3 resulted in the upregulation of AGAP2-AS1 in psoriasis. AGAP2-AS1 functioned as a competitive endogenous RNA by sponging miR-424–5p to upregulate AKT3, activate AKT/mTOR pathway, as well as promote cell proliferation in keratinocytes. Conclusion: AGAP2-AS1 is upregulated in the skin tissue of psoriasis patients and m 6 A methylation was involved in its upregulation. AGAP2-AS1 promotes keratinocyte proliferation through miR-424–5p/AKT/mTOR axis and may be a promising target for psoriasis therapy.