Structure based innovative approach to analyze aptaprobe–GPC3 complexes in hepatocellular carcinoma
Abstract Background Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, is a biomarker of hepatocellular carcinoma (HCC) progression. Aptamers specifically binding to target biomolecules have recently emerged as clinical disease diagnosis targets. Here, we describe 3D structure-based a...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-022-01391-z |
| _version_ | 1811299191424548864 |
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| author | Woo-Ri Shin Dae-Young Park Ji Hun Kim Jin-Pyo Lee Nguyen Quang Thai In-Hwan Oh Simranjeet Singh Sekhon Wooil Choi Sung Yeon Kim Byung-Kwan Cho Sun Chang Kim Jiho Min Ji-Young Ahn Yang-Hoon Kim |
| author_facet | Woo-Ri Shin Dae-Young Park Ji Hun Kim Jin-Pyo Lee Nguyen Quang Thai In-Hwan Oh Simranjeet Singh Sekhon Wooil Choi Sung Yeon Kim Byung-Kwan Cho Sun Chang Kim Jiho Min Ji-Young Ahn Yang-Hoon Kim |
| author_sort | Woo-Ri Shin |
| collection | DOAJ |
| description | Abstract Background Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, is a biomarker of hepatocellular carcinoma (HCC) progression. Aptamers specifically binding to target biomolecules have recently emerged as clinical disease diagnosis targets. Here, we describe 3D structure-based aptaprobe platforms for detecting GPC3, such as aptablotting, aptaprobe-based sandwich assay (ALISA), and aptaprobe-based imaging analysis. Results For preparing the aptaprobe–GPC3 platforms, we obtained 12 high affinity aptamer candidates (GPC3_1 to GPC3_12) that specifically bind to target GPC3 molecules. Structure-based molecular interactions identified distinct aptatopic residues responsible for binding to the paratopic nucleotide sequences (nt-paratope) of GPC3 aptaprobes. Sandwichable and overlapped aptaprobes were selected through structural analysis. The aptaprobe specificity for using in HCC diagnostics were verified through Aptablotting and ALISA. Moreover, aptaprobe-based imaging showed that the binding property of GPC3_3 and their GPC3 specificity were maintained in HCC xenograft models, which may indicate a new HCC imaging diagnosis. Conclusion Aptaprobe has the potential to be used as an affinity reagent to detect the target in vivo and in vitro diagnosing system. Graphical Abstract |
| first_indexed | 2024-04-13T06:31:35Z |
| format | Article |
| id | doaj.art-020512c046144a49a60ac23eabe54916 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-13T06:31:35Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-020512c046144a49a60ac23eabe549162022-12-22T02:58:06ZengBMCJournal of Nanobiotechnology1477-31552022-04-0120111710.1186/s12951-022-01391-zStructure based innovative approach to analyze aptaprobe–GPC3 complexes in hepatocellular carcinomaWoo-Ri Shin0Dae-Young Park1Ji Hun Kim2Jin-Pyo Lee3Nguyen Quang Thai4In-Hwan Oh5Simranjeet Singh Sekhon6Wooil Choi7Sung Yeon Kim8Byung-Kwan Cho9Sun Chang Kim10Jiho Min11Ji-Young Ahn12Yang-Hoon Kim13School of Biological Sciences, Chungbuk National UniversitySchool of Biological Sciences, Chungbuk National UniversityDepartment of Biological Sciences, Korea Advanced Institute of Science and TechnologySchool of Biological Sciences, Chungbuk National UniversitySchool of Biological Sciences, Chungbuk National UniversitySchool of Biological Sciences, Chungbuk National UniversitySchool of Biological Sciences, Chungbuk National UniversityGraduate School of Semiconductor and Chemical Engineering, Jeonbuk National UniversityCollege of Pharmacy, Wonkwang UniversityDepartment of Biological Sciences, Korea Advanced Institute of Science and TechnologyDepartment of Biological Sciences, Korea Advanced Institute of Science and TechnologyGraduate School of Semiconductor and Chemical Engineering, Jeonbuk National UniversitySchool of Biological Sciences, Chungbuk National UniversitySchool of Biological Sciences, Chungbuk National UniversityAbstract Background Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, is a biomarker of hepatocellular carcinoma (HCC) progression. Aptamers specifically binding to target biomolecules have recently emerged as clinical disease diagnosis targets. Here, we describe 3D structure-based aptaprobe platforms for detecting GPC3, such as aptablotting, aptaprobe-based sandwich assay (ALISA), and aptaprobe-based imaging analysis. Results For preparing the aptaprobe–GPC3 platforms, we obtained 12 high affinity aptamer candidates (GPC3_1 to GPC3_12) that specifically bind to target GPC3 molecules. Structure-based molecular interactions identified distinct aptatopic residues responsible for binding to the paratopic nucleotide sequences (nt-paratope) of GPC3 aptaprobes. Sandwichable and overlapped aptaprobes were selected through structural analysis. The aptaprobe specificity for using in HCC diagnostics were verified through Aptablotting and ALISA. Moreover, aptaprobe-based imaging showed that the binding property of GPC3_3 and their GPC3 specificity were maintained in HCC xenograft models, which may indicate a new HCC imaging diagnosis. Conclusion Aptaprobe has the potential to be used as an affinity reagent to detect the target in vivo and in vitro diagnosing system. Graphical Abstracthttps://doi.org/10.1186/s12951-022-01391-zGlypican-3Hepatocellular carcinomaCancer diagnosisAptaprobeStructure-based molecular interactionAptablotting |
| spellingShingle | Woo-Ri Shin Dae-Young Park Ji Hun Kim Jin-Pyo Lee Nguyen Quang Thai In-Hwan Oh Simranjeet Singh Sekhon Wooil Choi Sung Yeon Kim Byung-Kwan Cho Sun Chang Kim Jiho Min Ji-Young Ahn Yang-Hoon Kim Structure based innovative approach to analyze aptaprobe–GPC3 complexes in hepatocellular carcinoma Journal of Nanobiotechnology Glypican-3 Hepatocellular carcinoma Cancer diagnosis Aptaprobe Structure-based molecular interaction Aptablotting |
| title | Structure based innovative approach to analyze aptaprobe–GPC3 complexes in hepatocellular carcinoma |
| title_full | Structure based innovative approach to analyze aptaprobe–GPC3 complexes in hepatocellular carcinoma |
| title_fullStr | Structure based innovative approach to analyze aptaprobe–GPC3 complexes in hepatocellular carcinoma |
| title_full_unstemmed | Structure based innovative approach to analyze aptaprobe–GPC3 complexes in hepatocellular carcinoma |
| title_short | Structure based innovative approach to analyze aptaprobe–GPC3 complexes in hepatocellular carcinoma |
| title_sort | structure based innovative approach to analyze aptaprobe gpc3 complexes in hepatocellular carcinoma |
| topic | Glypican-3 Hepatocellular carcinoma Cancer diagnosis Aptaprobe Structure-based molecular interaction Aptablotting |
| url | https://doi.org/10.1186/s12951-022-01391-z |
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