Specific inhibition of FGF5-induced cell proliferation by RNA aptamers.

Affiliation

Amano R(1), Namekata M(2), Horiuchi M(3), Saso M(1), Yanagisawa T(1), Tanaka Y(4), Ghani FI(2), Yamamoto M(2), Sakamoto T(5).
Author information:
(1)Department of Life Science, Faculty of Advanced Engineering, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino-shi, Chiba, 275-0016, Japan.
(2)Advangen Inc, 4-6-3 Kashiwa, Kashiwa-shi, Chiba, 277-0005, Japan.
(3)Faculty of Pharmaceutical Science, Health Sciences University of Hokkaido, 1757 Kanazawa, Toubetsu, Ishikari, Hokkaido, 061-0293, Japan.
(4)Facility for RI Research and Education, Instrumental Analysis Center, Research Initiatives and Promotion Organization, Yokohama National University, 79-5 Tokiwadai, hodogaya-ku, Yokohama, 240-8501, Japan.
(5)Department of Life Science, Faculty of Advanced Engineering, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino-shi, Chiba, 275-0016, Japan. [Email]

Abstract

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 (Kd = 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 (Kd = 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.