5′tiRNA-Glu-TTC targets TRPV3 and activates the PI3K/AKT signaling pathway to modulate skin photoaging

作者：Zhuohong Xu, Lihao Liu, Xiaoxi Dai, Xuyue Zhou, Lihao Chen, Hongying Chen, Chao Luan, Dan Huang, Jiaan Zhang, Yu Hu, Kun Chen, Heng Gu · 发表于：Non-coding RNA Research · 年份：2025 · DOI：10.1016/j.ncrna.2025.07.004 · 被引用次数：4 · 研究领域：Skin Protection and Aging、melanin and skin pigmentation、Genomics, phytochemicals, and oxidative stress

tRNA-derived small RNAs (tsRNAs), a class of non-coding RNAs (ncRNAs), have garnered increasing research interest for their potential roles in various biological processes. Among these, 5'tiRNA-Glu-TTC has been implicated in aging, but its role in skin photoaging remains elusive. This study aimed to elucidate the impact of 5'tiRNA-Glu-TTC on skin photoaging. RT-qPCR analysis revealed that 5'tiRNA-Glu-TTC expression increased in human dermal fibroblasts (HDFs), human skin tissues, and mouse skin tissues following UVB irradiation. In HDFs, transfection of a 5'tiRNA-Glu-TTC mimic induced photoaging phenotypes, while its inhibitor alleviated UVB-induced photoaging. This study found that 5'tiRNA-Glu-TTC participates in photoaging through binding to TRPV3. Overexpression of TRPV3 rescued the photoaging effects induced by the 5'tiRNA-Glu-TTC mimic. Furthermore, 5'tiRNA-Glu-TTC influences photoaging also by activating the PI3K/AKT signaling pathway, an effect that was reversed by TRPV3 overexpression. In vivo studies in nude mice showed that intradermal injection of 5'tiRNA-Glu-TTC adeno-associated virus alleviated UVB-induced skin aging phenotypes, including epidermal thickening, dermal collagen reduction, and increased transepidermal water loss (TEWL). Collectively, our findings demonstrate that 5'tiRNA-Glu-TTC mediates photoaging by targeting TRPV3 and activating the PI3K/AKT pathway.