Wang Wei, Zheng Yan, Jia Jinjing, Li Changji, Duan Qiqi, Li Ruilian, Wang Xin, Shao Yongping, Chen Caifeng, Yan Huling
Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an, Shaanxi 710004, P.R. China.
Exp Ther Med. 2017 Jul;14(1):499-506. doi: 10.3892/etm.2017.4546. Epub 2017 Jun 6.
Antimicrobial peptide LL-37 serves a function in the host defense against microbial invasion, and also regulates cell proliferation, immune activity and angiogenesis. Previous studies have reported that LL-37 participates in the development of numerous tumour types, such as ovarian cancer, lung cancer, melanoma and breast cancer. However, the function of LL-37 in the development of skin squamous cell carcinoma (SCC) has not yet been fully elucidated. The aim of the current study was to investigate how LL-37 promotes the expression of Y-box binding protein 1 (YB-1) in SCC. Short interfering RNA (siRNA) was used to inhibit the expression of YB-1, and MTT and Transwell migration assays were used to evaluate the effect of reduced YB-1 on the viability and invasion of A431 cells. A431 cells were stimulated with LL-37, and quantitative polymerase chain reaction, immunofluorescence and western blot analyses were used to detect changes in YB-1 expression. Mitogen-activated protein kinase kinase, mitogen-activated protein kinase and nuclear factor (NF)-κB signaling pathway inhibitors were also used to evaluate the mechanism of LL-37-induced YB-1 protein expression. It was found that YB-1 expression was increased in SCC tissue compared with normal tissue. Inhibiting YB-1 expression using siRNA significantly reduced the viability and suppressed the invasion of tumour cells (P<0.05 for both). LL-37 treatment at 0.05 µg/ml for 24 or 48 h significantly promoted YB-1 protein expression (P<0.05), and this was dependent on the NF-κB signaling pathway. In conclusion, the current study demonstrated that by upregulating the expression of YB-1, LL-37 can promote the occurrence and development of SCC, and this process involves the NF-κB signaling pathway.
抗菌肽LL-37在宿主抵御微生物入侵中发挥作用，还可调节细胞增殖、免疫活性和血管生成。既往研究报道LL-37参与多种肿瘤类型的发生发展，如卵巢癌、肺癌、黑色素瘤和乳腺癌。然而，LL-37在皮肤鳞状细胞癌（SCC）发生发展中的作用尚未完全阐明。本研究旨在探讨LL-37如何促进SCC中Y盒结合蛋白1（YB-1）的表达。使用小干扰RNA（siRNA）抑制YB-1的表达，并采用MTT和Transwell迁移试验评估YB-1表达降低对A431细胞活力和侵袭的影响。用LL-37刺激A431细胞，采用定量聚合酶链反应、免疫荧光和蛋白质印迹分析检测YB-1表达的变化。还使用丝裂原活化蛋白激酶激酶、丝裂原活化蛋白激酶和核因子（NF）-κB信号通路抑制剂评估LL-37诱导YB-1蛋白表达的机制。结果发现，与正常组织相比，SCC组织中YB-1表达增加。使用siRNA抑制YB-1表达可显著降低肿瘤细胞的活力并抑制其侵袭（两者P均<0.05）。0.05μg/ml的LL-37处理24或48小时可显著促进YB-1蛋白表达（P<0.05），且这一过程依赖于NF-κB信号通路。总之，本研究表明，LL-37可通过上调YB-1的表达促进SCC的发生发展，且这一过程涉及NF-κB信号通路。
