N 6 -methyladenosine-modified long non-coding RNA AGAP2-AS1 promotes psoriasis pathogenesis via miR-424–5p/AKT3 axis

Psoriasis is a chronic, complicated, and recurrent inflammatory skin disease. However, the precise molecular mechanisms remain largely elusive and the present treatment is unsatisfactory. 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. 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. 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. 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.