Identification of the role of autophagy-related TNFSF10/ hsa-let-7a-5p axis in vitiligo development and potential herbs exploring based on a bioinformatics analysis

Wenwen Wang; Danfeng Xu; Youming Huang; Xiaohua Tao; Yibin Fan; Zhiming Li; Xiaoxia Ding

doi:10.1016/j.heliyon.2023.e23220

Identification of the role of autophagy-related TNFSF10/ hsa-let-7a-5p axis in vitiligo development and potential herbs exploring based on a bioinformatics analysis

Heliyon. 2023 Dec 3;9(12):e23220. doi: 10.1016/j.heliyon.2023.e23220. eCollection 2023 Dec.

Authors

Wenwen Wang^{1

2}, Danfeng Xu¹, Youming Huang¹, Xiaohua Tao¹, Yibin Fan¹, Zhiming Li², Xiaoxia Ding¹

Affiliations

¹ Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People's Hospital(Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310000, China.
² Department of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.

Abstract

Background: Vitiligo is a common clinical disorder caused by the destruction of epidermal melanocytes, which is often associated with autoimmune mechanisms. Autophagy plays a crucial role in maintaining cellular homeostasis and exhibits close associations with various autoimmune disorders. While dysautophagy of melanocytes is associated with vitiligo pathogenesis, there is a lack of studies on autophagy-related genes (ARGs) in blood samples from individuals with vitiligo.

Methods: Blood samples from individuals with vitiligo and healthy controls were compared to identify differentially expressed genes (DEGs), which were subsequently subjected to further analysis. Then, miRNAs correlated with core genes were predicted by five distinct online tools, and those miRNAs that appeared in three or more tools at the same time were chosen for further enrichment analysis. Furthermore, in vitro experiments of targeting core genes were conducted.

Results: The results showed that there were a total of 30 ARGs among DEGs, with 13 up-regulated genes and 17 down-regulated genes. Based on the functional enrichment analysis of DEGs and projected miRNAs, we hypothesized that autophagy and apoptosis may synergistically contribute to the progression of vitiligo, with the TNFSF10/hsa-let-7a-5p axis potentially playing an important role that should not be ignored. In addition, epigallocatechin-3-gallate (EGCG) was found to be the common component in BAI GUO, CHA YE, and MEI ZHOU JIN LV MEI, which were discovered to be potential in vitiligo treatment by inducing cell autophagy and apoptosis targeting TNFSF10.

Conclusion: It was the first time that TNFSF/hsa-let-7a-5p was discovered to be involved in the development of vitiligo through autophagy and apoptosis. Meanwhile, we observed that BAI GUO, CHA YE, and MEI ZHOU JIN LV MEI were promising to treat vitiligo by regulating autophagy and apoptosis via TNFSF10. These findings could lead to new directions for investigating the pathogenesis and therapy of vitiligo.

Keywords: Apoptosis; Autophagy; Bioinformatics; Herbs; TNFSF10; Vitiligo.