Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Guangzhou road 300#, Nanjing, Jiangsu province, China PR.
Int J Biol Sci. 2013 Aug 9;9(7):743-52. doi: 10.7150/ijbs.5345. eCollection 2013.
Previous studies showed that several miRNAs can regulate pathways involved in UVB-induced premature senescence and response to ultraviolet irradiation. It has also been reported that miR-34c-5p may be involved in senescence-related mechanisms. We propose that miR-34c-5p may play a crucial role in senescence of normal human primary dermal fibroblasts. Here, we explored the roles of miR-34c-5p in UVB-induced premature senescence on dermal fibroblasts. MiR-34c-5p expression was increased in dermal fibroblasts after repeated subcytotoxic UVB treatments. Underexpression of miR-34c-5p in dermal fibroblasts led to a marked delay of many senescent phenotypes induced by repeated UVB treatments. Furthermore, underexpression of miR-34c-5p in dermal fibroblasts can antagonize the alteration of G1-arrested fibroblasts. Moreover, E2F3, which can inactivate p53 pathway and play a role in cell cycle progression, is a down-stream target of miR-34c-5p. Forced down-expression of miR-34c-5p decreased the expression of UVB-SIPS induced P21 and P53 at both mRNA and protein levels. Our data demonstrated that down-regulation of miR-34c-5p can protect human primary dermal fibroblasts from UVB-induced premature senescence via regulations of some senescence-related molecules.
先前的研究表明，几种 miRNA 可以调控与 UVB 诱导的衰老和对紫外线照射的反应相关的途径。据报道，miR-34c-5p 可能参与衰老相关的机制。我们提出 miR-34c-5p 可能在正常人原代真皮成纤维细胞的衰老中发挥关键作用。在这里，我们探讨了 miR-34c-5p 在 UVB 诱导的真皮成纤维细胞过早衰老中的作用。重复亚细胞毒性 UVB 处理后，真皮成纤维细胞中的 miR-34c-5p 表达增加。真皮成纤维细胞中 miR-34c-5p 的表达下调导致许多由重复 UVB 处理诱导的衰老表型明显延迟。此外，真皮成纤维细胞中 miR-34c-5p 的表达下调可以拮抗 G1 期停滞的成纤维细胞的改变。此外，E2F3 可以使 p53 通路失活，并在细胞周期进展中发挥作用，是 miR-34c-5p 的下游靶标。强制下调 miR-34c-5p 的表达可降低 UVB-SIPS 诱导的 P21 和 P53 在 mRNA 和蛋白水平的表达。我们的数据表明，miR-34c-5p 的下调可以通过调节一些衰老相关分子来保护人原代真皮成纤维细胞免受 UVB 诱导的过早衰老。
