Long noncoding RNA LINC01435 impedes diabetic wound healing by facilitating YY1-mediated HDAC8 expression

Wan Fu; Diefei Liang; Xiaoying Wu; Hongxing Chen; Xiaosi Hong; Jiahuan Wang; Tianxin Zhu; Tingting Zeng; Weijie Lin; Sifan Chen; Li Yan; Meng Ren

doi:10.1016/j.isci.2022.104006

Long noncoding RNA LINC01435 impedes diabetic wound healing by facilitating YY1-mediated HDAC8 expression

iScience. 2022 Mar 1;25(4):104006. doi: 10.1016/j.isci.2022.104006. eCollection 2022 Apr 15.

Authors

Wan Fu^{1

2}, Diefei Liang^{1

2}, Xiaoying Wu^{1

2}, Hongxing Chen^{1

2}, Xiaosi Hong^{1

2}, Jiahuan Wang^{1

2}, Tianxin Zhu^{1

2}, Tingting Zeng^{1

2}, Weijie Lin^{2

3}, Sifan Chen^{2

3}, Li Yan^{1

2}, Meng Ren^{1

2}

Affiliations

¹ Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou 510120, China.
² Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou 510120, China.
³ Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.

Abstract

Abnormal interactions between skin cells play an important role in the dysregulation of diabetic wound recovery. Exosomes are cell-derived lipid nanoparticles that transport messages between cells, and isolating and identifying potential therapeutic noncoding RNAs from exosomes is very important. We demonstrated that treatment with Exos from high glucose-pretreated immortalized human epidermal (HaCaT) cells (HG-Exos) could delay the wound healing process in diabetic mice. Further analysis indicated the Exo-mediated uptake of LINC01435 in recipient human umbilical vein endothelial cells (HUVECs) changes the subcellular localization of the transcription factor Yin Yang 1 (YY1) and cooperates with YY1 to upregulate the expression of histone deacetylases (HDACs)8, resulting in decreased tube formation and ability of HUVECs to migrate, thus angiogenesis was inhibited. These results suggest that LINC01435/YY1/HDAC8 may be an important signaling pathway affecting the recovery of diabetic wounds, which makes it a potential target for the treatment of diabetic foot ulcers.

Keywords: Biological sciences; Cell biology; Molecular biology.