ILF2 Contributes to Hyperproliferation of Keratinocytes and Skin Inflammation in a KLHDC7B-DT-Dependent Manner in Psoriasis

Xiran Yin; Zhenxian Yang; Mingsheng Zhu; Cheng Chen; Shan Huang; Xueqing Li; Hua Zhong; He Wen; Qing Sun; Xiaojing Yu; Jianjun Yan

doi:10.3389/fgene.2022.890624

ILF2 Contributes to Hyperproliferation of Keratinocytes and Skin Inflammation in a KLHDC7B-DT-Dependent Manner in Psoriasis

Front Genet. 2022 May 2:13:890624. doi: 10.3389/fgene.2022.890624. eCollection 2022.

Authors

Xiran Yin^{1

2}, Zhenxian Yang^{1

2}, Mingsheng Zhu³, Cheng Chen^{1

2}, Shan Huang^{1

2}, Xueqing Li^{1

2}, Hua Zhong^{1

2}, He Wen^{1

2}, Qing Sun^{1

2}, Xiaojing Yu^{1

2}, Jianjun Yan^{1

2}

Affiliations

¹ Department of Dermatology, Qilu Hospital, Shandong University, Jinan, China.
² Laboratory of Basic Medical Science, Qilu Hospital, Shandong University, Jinan, China.
³ Department of Hand and Foot surgery, Shandong Provincial Hospital, Jinan, China.

Abstract

Background: The extensive involvement of interleukin enhancer binding factor 2 (ILF2) in RNA stability and the inflammatory response is well documented. Aberrant long noncoding RNA (lncRNA) expression contributes to the pathogenesis of psoriasis. However, little is known about the role of ILF2 in psoriasis. Objective: To investigate the role of ILF2 and KLHDC7B-DT in psoriasis. Methods: LncRNA expression in psoriatic tissues was measured by lncRNA microarray and qRT-PCR. Normal human epidermal keratinocytes (NHEKs), HaCaT cells, and Ker-CT cells stimulated with M5 (IL-17A, IL-22, IL-1α, oncostatin M, and TNF-α) were used to establish a psoriasis model in vitro. Fluorescence in situ hybridization was used to detect the distribution of KLHDC7B-DT and ILF2 in keratinocytes. The proliferative effects of KLHDC7B-DT and ILF2 on keratinocytes were demonstrated by EdU assay and flow cytometry. ELISA was used to detect the secretion levels of cytokines. RNA pull-down and RNA immunoprecipitation (RIP) were used to detect the direct binding of KLHDC7B-DT with ILF2. Western blotting was used to detect the proteins related to STAT3/JNK signalling pathways. Results: ILF2 and KLHDC7B-DT were significantly overexpressed in psoriatic tissues and M5-induced keratinocytes. KLHDC7B-DT promoted the proliferation of keratinocytes and induced the secretion of IL-6 and IL-8. KLHDC7B-DT could directly bind to ILF2 and activate the STAT3 and JNK signalling pathways. KLHDC7B-DT expression was regulated by ILF2. M5-induced proliferation and inflammatory cytokine secretion in keratinocytes was inhibited after ILF2 knockdown. Furthermore, we found that ILF2 promoted keratinocyte proliferation and the inflammatory response in a KLHDC7B-DT-dependent manner. Conclusions: ILF2 and KLHDC7B-DT are involved in the hyperproliferation of keratinocytes and skin inflammation in psoriasis. In addition, ILF2 functions in a KLHDC7B-DT-dependent manner.

Keywords: ILF2; KLHDC7B-DT; inflammation; proliferation; psoriasis.