Peng Yating, Song Xiaojing, Zheng Yue, Wang Xinyi, Lai Wei
Department of Dermatology and Venereology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
Department of Dermatology and Venereology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
Biochem Biophys Res Commun. 2017 Apr 29;486(2):277-284. doi: 10.1016/j.bbrc.2017.03.028. Epub 2017 Mar 9.
Production of type I collagen declines is a main characteristic during photoaging, but the mechanism is still not fully understood. Circular RNAs (circRNAs) are a class of newly identified non-coding RNAs with regulatory potency by sequestering miRNAs like a sponge. It's more stable than linear RNAs, and would be a useful tool for regulation of gene expression. However, the role of circRNAs in collagen expression during photoaging is still unclear. Here we performed deep sequencing of RNA generated from UVA irradiated and no irradiated human dermal fibroblasts (HDFs) and identified 29 significantly differentially expressed circRNAs (fold change ≥ 1.5, P < 0.05), 12 circRNAs were up-regulated and 17 circRNAs were down-regulated.3 most differentially expressed circRNAs were verified by qRT-PCR and the down-regulated circCOL3A1-859267 exhibited the most significantly altered in photoaged HDFs. Overexpression of circCOL3A1-859267 inhibited UVA-induced decrease of type I collagen expression and silencing of it reduced type I collagen intensity. Via a bioinformatic method, 44 miRNAs were predicted to binding with circCOL3A1-859267, 5 of them have been confirmed or predicted to interact with type I collagen. This study show that circCOL3A1-859267 regulate type I collagen expression in photoaged HDFs, suggesting it may be a novel target for interfering photoaging.
I型胶原蛋白生成减少是光老化的主要特征之一,但其机制仍未完全明确。环状RNA(circRNA)是一类新发现的非编码RNA,具有像海绵一样吸附微小RNA(miRNA)的调控能力。它比线性RNA更稳定,可能成为调控基因表达的有用工具。然而,circRNA在光老化过程中对胶原蛋白表达的作用仍不清楚。在此,我们对紫外线照射和未照射的人皮肤成纤维细胞(HDF)产生的RNA进行了深度测序,鉴定出29个显著差异表达的circRNA(倍数变化≥1.5,P<0.05),其中12个circRNA上调,17个circRNA下调。通过qRT-PCR验证了3个差异最显著的circRNA,下调的circCOL3A1-859267在光老化的HDF中变化最为显著。circCOL3A1-859267的过表达抑制了紫外线诱导的I型胶原蛋白表达下降,而对其进行沉默则降低了I型胶原蛋白的强度。通过生物信息学方法,预测有44个miRNA与circCOL3A1-859267结合,其中5个已被证实或预测与I型胶原蛋白相互作用。本研究表明,circCOL3A1-859267在光老化的HDF中调节I型胶原蛋白的表达,提示其可能是干预光老化的新靶点。