LncRNA AGXT2L1-2:2 facilitates keratinocytes proliferation and inhibits apoptosis by interacting with estrogen-related receptor alpha in psoriasis

Abstract

Our previous studies have revealed that long noncoding RNA (lncRNA) AGXT2L1-2:2 was highly expressed in keratinocytes of psoriasis. However, the functions of lnc-AGXT2L1-2:2 in keratinocytes remain unknown. Meanwhile, co-expression network analysis indicated lnc-AGXT2L1-2:2 could interact with estrogen-related receptor alpha (ERRα). In this study, interleukin (IL)-17A could stimulate the production of lnc-AGXT2L1-2:2 in keratinocytes, thus establishing an in vitro cellular model of psoriasis. Lnc-AGXT2L1-2:2 was overexpressed using lentiviral-vector and ERRα was downregulated with small interfering RNA. Then the effects of lnc-AGXT2L1-2:2 and ERRα on viability, apoptosis, and cell cycle in IL-17A-stimulated keratinocytes were assessed by CCK-8, EdU assay, and flow cytometry. We found that lnc-AGXT2L1-2:2 and ERRα both resulted in higher proliferation ability, lower apoptosis rates, and reduction of G0/G1 phase proportion. Furthermore, lnc-AGXT2L1-2:2 could promote the expression of ERRα and siERRα antagonized the effects of lnc-AGXT2L1-2:2 on the phenotypes above in IL-17A-induced keratinocytes. In conclusion, lnc-AGXT2L1-2:2 was found to promote keratinocytes proliferation, inhibit cell apoptosis and the effects of lnc-AGXT2L1-2:2 on keratinocytes are dependent on ERRα.

Keywords: ERRα; IL-17A; LncRNA AGXT2L1-2:2; Proliferation; Psoriasis.