Metastasis is the leading cause of death from cutaneous melanoma.Identifying metastasisrelated targets and developing corresponding therapeutic strategies are major areas of focus.While functional genomics strategies ...Metastasis is the leading cause of death from cutaneous melanoma.Identifying metastasisrelated targets and developing corresponding therapeutic strategies are major areas of focus.While functional genomics strategies provide powerful tools for target discovery,investigations at the protein level can directly decode the bioactive epitopes on functional proteins.Aptamers present a promising avenue as they can explore membrane proteomes and have the potential to interfere with cell function.Herein,we developed a target and epitope discovery platform,termed functional aptamer evolution-enabled target identification(FAETI),by integrating affinity aptamer acquisition with phenotype screening and target protein identification.Utilizing the aptamer XH3C,which was screened for its migration-inhibitory function,we identified the Chondroitin Sulfate Proteoglycan 4(CSPG4),as a potential target involved in melanoma migration.Further evidence demonstrated that XH3C induces cytoskeletal rearrangement by blocking the interaction between the bioactive epitope of CSPG4 and integrin a4.Taken together,our study demonstrates the robustness of aptamer-based molecular tools for target and epitope discovery.Additionally,XH3C is an affinity and functional molecule that selectively binds to a unique epitope on CSPG4,enabling the development of innovative therapeutic strategies.展开更多
基金湖南省自然科学基金(编号:10JJ7003)资助supported by the National Natural Science Foundation of China(Nos.30871282,30871365,81172189,81171930,and 81272298)+2 种基金the Fok Ying Tong Education Foundation(121036)the Fundamental Research Funds for the Central South Universities(2011JQ020)the Mittal Innovative Entrepreneurial Project ofCentral South University(11MX27)~~
基金financially supported by the National Key Research&Development Program of China(Grant No.2022YFA1304500)the National Natural Science Foundation of China(Grant No.22227805,22374004)+2 种基金Excellent Young Scientists Fund Program(Overseas)Clinical Medicine Plus X-Young Scholars Project of Peking Universitythe Fundamental Research Funds for the Central Universities(No.PKU2024LCXQ026,China).
文摘Metastasis is the leading cause of death from cutaneous melanoma.Identifying metastasisrelated targets and developing corresponding therapeutic strategies are major areas of focus.While functional genomics strategies provide powerful tools for target discovery,investigations at the protein level can directly decode the bioactive epitopes on functional proteins.Aptamers present a promising avenue as they can explore membrane proteomes and have the potential to interfere with cell function.Herein,we developed a target and epitope discovery platform,termed functional aptamer evolution-enabled target identification(FAETI),by integrating affinity aptamer acquisition with phenotype screening and target protein identification.Utilizing the aptamer XH3C,which was screened for its migration-inhibitory function,we identified the Chondroitin Sulfate Proteoglycan 4(CSPG4),as a potential target involved in melanoma migration.Further evidence demonstrated that XH3C induces cytoskeletal rearrangement by blocking the interaction between the bioactive epitope of CSPG4 and integrin a4.Taken together,our study demonstrates the robustness of aptamer-based molecular tools for target and epitope discovery.Additionally,XH3C is an affinity and functional molecule that selectively binds to a unique epitope on CSPG4,enabling the development of innovative therapeutic strategies.
