A Pilot Study for Protective Roles of tRNA-Derived Small RNA tRF-Ile-AAT-019 in Pathological Progression of Psoriasis

Psoriasis is a chronic recurrent inflammatory skin disease that is characterized by abnormal proliferation and differentiation of keratinocytes (KCs), angiogenesis and skin inflammation. tRNA-derived small RNA (tsRNA), including tRNA halves and tRNA fragments (tRFs), is a novel class of short non-coding RNA, possessing regulatory functions in many diseases. However, its role in the pathological development of psoriasis has been unknown. In this pilot study, we conducted small RNA sequencing to screen differentially expressed tRFs in psoriatic skin lesions as compared with normal controls. We found 130 upregulated and 104 downregulated tRFs, among which downregulation of tRF-Ile-AAT-019 in psoriatic skin lesions was further confirmed. Bioinformatics analysis by TargetScan and Miranda algorithms revealed that tRF-Ile-AAT-019 might target SERPINE1, thus regulating HIF-1a signaling pathway. We next showed that increased tRF-Ile-AAT-019 could downregulate expressions of SERPINE1, HIF-1a and vascular proliferative markers such as CD34, CD31, Factor VIII, and VEGF, but upregulate expressions of KCs differentiation markers including Keratin1 and Involucrin. Our data suggest that tRF-Ile-AAT-019 plays a protective role in the pathological progression of psoriasis via targeting SERPINE1 and blocking HIF-1a signaling pathway, leading to control KCs differentiation and vascular proliferation. This data provides a potential novel targeting pathway for the disease treatment. Overall design: The tRF/tiRNAs-Seq analysis was used to assess the expression levels of tRF/tiRNAs in skin lesions of 3 psoriasis patients (P) and 3 normal volunteers (N).