| Summary: | 碩士 === 國立成功大學 === 口腔醫學研究所 === 102 === Aptamers are short DNA or RNA sequence that can bind to specific sites on proteins through its secondary conformation and structure. The binding of the aptamer to the protein can result in blockage of specific protein functions. Previous studies from our group have identified aptamers AP-27, AP-39, and AP-74 which possess high binding affinity for galectin-1 (Gal-1), a member of galectin family that has a carbohydrate recognition domain (CRD) to bind to β-galactosides. Gal-1 plays a critical role in the regulation of cell adhesion, migration, tumorigenesis and promoting cancer cells metastasis. Furthermore, we also found that Gal-1 influences the several biological functions of normal cells such as promoting fibroblast proliferation and activation. Activation of fibroblasts plays important role in several physiological and pathological processes such as wound healing and liver fibrosis. We have demonstrated that AP-27 and AP-39 dose-dependently inhibit Gal-1-induced oral cancer cell adhesion. In this study, we found that the aptamers efficiently rescued Gal-1-activated fibroblast migration and proliferation. These aptamers, especially AP-74, decreased Gal-1-induced phosphorylation of Smad3 in fibroblasts. On the other hand, we also found that these aptamers inhibited Gal-1-induced lung cancer cell migration and might through inhibiting Akt/mTOR signaling pathway. In the future, the Gal-1 aptamers will be optimized by screening a custom aptamer array chip to search out the effective region of Gal-1 aptamers for costing down and further applications. The development of Gal-1 aptamer-based therapeutics may provide unique clinical opportunities for diseases associated with fibroblast activation, and preventing cancer cell metastasis.
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