RNA 适体特异性抑制 FGF5 诱导的细胞增殖。
Specific inhibition of FGF5-induced cell proliferation by RNA aptamers.
机构信息
Department of Life Science, Faculty of Advanced Engineering, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino-shi, Chiba, 275-0016, Japan.
Advangen Inc, 4-6-3 Kashiwa, Kashiwa-shi, Chiba, 277-0005, Japan.
出版信息
Sci Rep. 2021 Feb 3;11(1):2976. doi: 10.1038/s41598-021-82350-w.
Fibroblast growth factor 5 (FGF5) is a crucial regulator of hair growth and an oncogenic factor in several human cancers. To generate FGF5 inhibitors, we performed Systematic Evolution of Ligands by EXponential enrichment and obtained novel RNA aptamers that have high affinity to human FGF5. These aptamers inhibited FGF5-induced cell proliferation, but did not inhibit FGF2-induced cell proliferation. Surface plasmon resonance demonstrated that one of the aptamers, F5f1, binds to FGF5 tightly (K = 0.7 ± 0.2 nM), but did not fully to FGF1, FGF2, FGF4, FGF6, or FGFR1. Based on sequence and secondary structure similarities of the aptamers, we generated the truncated aptamer, F5f1_56, which has higher affinity (K = 0.118 ± 0.003 nM) than the original F5f1. Since the aptamers have high affinity and specificity to FGF5 and inhibit FGF5-induced cell proliferation, they may be candidates for therapeutic use with FGF5-related diseases or hair disorders.
成纤维细胞生长因子 5 (FGF5) 是毛发生长的关键调节因子，也是几种人类癌症中的致癌因子。为了生成 FGF5 抑制剂，我们进行了指数富集的配体系统进化，获得了对人 FGF5 具有高亲和力的新型 RNA 适体。这些适体抑制了 FGF5 诱导的细胞增殖，但不抑制 FGF2 诱导的细胞增殖。表面等离子体共振实验表明，其中一种适体 F5f1 与 FGF5 紧密结合（Kd=0.7±0.2 nM），但与 FGF1、FGF2、FGF4、FGF6 或 FGFR1 不完全结合。基于适体的序列和二级结构相似性，我们生成了截断的适体 F5f1_56，它比原始 F5f1 具有更高的亲和力（Kd=0.118±0.003 nM）。由于适体对 FGF5 具有高亲和力和特异性，并抑制 FGF5 诱导的细胞增殖，它们可能成为与 FGF5 相关疾病或毛发紊乱相关的治疗用途的候选物。
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