File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Novel RNA aptamers targeting gastrointestinal cancer biomarkers CEA, CA50 and CA72-4 with superior affinity and specificity

TitleNovel RNA aptamers targeting gastrointestinal cancer biomarkers CEA, CA50 and CA72-4 with superior affinity and specificity
Authors
KeywordsAGS cell line
binding affinity
cell growth
cell viability
controlled study
Issue Date2018
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
PLoS One, 2018, v. 13 n. 10, p. article no. e0198980 How to Cite?
AbstractGastric cancer is the third most common cause of death from cancer in the world and it remains difficult to cure in Western countries, primarily because most patients present with advanced disease. Currently, CEA, CA50 and CA72-4 are commonly used as tumor markers for gastric cancer by immunoassays. However, the drawback and conundrum of immunoassay are the unceasing problem in standardization of quality of antibodies and time/ effort for the intensive production. Therefore, there is an urgent need for the development of a standardized assay to detect gastric cancer at the early stage. Aptamers are DNA or RNA oligonucleotides with structural domain which recognize ligands such as proteins with superior affinity and specificity when compared to antibodies. In this study, SELEX (Systematic Evolution of Ligands by Exponential enrichment) technique was adopted to screen a random 30mer RNA library for aptamers targeting CEA, CA50 and CA72-4 respectively. Combined with high-throughput sequencing, we identified 6 aptamers which specifically target for these three biomarkers of gastrointestinal cancer. Intriguingly, the predicted secondary structures of RNA aptamers from each antigen showed significant structural similarity, suggesting the structural recognition between the aptamers and the antigens. Moreover, we determined the dissociation constants of all the aptamers to their corresponding antigens by fluorescence spectroscopy, which further demonstrated high affinities between the aptamers and the antigens. In addition, immunostaining of gastric adenocarcinoma cell line AGS using CEA Aptamer probe showed positive fluorescent signal which proves the potential of the aptamer as a detection tool for gastric cancer. Furthermore, substantially decreased cell viability and growth were observed when human colorectal cell line LS-174T was transfected with each individual aptamers. Taking together, these novel RNA aptamers targeting gastrointestinal cancer biomarker CEA, CA50 and CA72-4 will aid further development and standardization of clinical diagnostic method with better sensitivity and specificity, and potentially future therapeutics development of gastric cancer.
Persistent Identifierhttp://hdl.handle.net/10722/274511
ISSN
2017 Impact Factor: 2.766
2015 SCImago Journal Rankings: 1.395

 

DC FieldValueLanguage
dc.contributor.authorPan, Q-
dc.contributor.authorLaw, COK-
dc.contributor.authorYung, MMH-
dc.contributor.authorHan, KC-
dc.contributor.authorPon, YL-
dc.contributor.authorLau, TCK-
dc.date.accessioned2019-08-18T15:03:08Z-
dc.date.available2019-08-18T15:03:08Z-
dc.date.issued2018-
dc.identifier.citationPLoS One, 2018, v. 13 n. 10, p. article no. e0198980-
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10722/274511-
dc.description.abstractGastric cancer is the third most common cause of death from cancer in the world and it remains difficult to cure in Western countries, primarily because most patients present with advanced disease. Currently, CEA, CA50 and CA72-4 are commonly used as tumor markers for gastric cancer by immunoassays. However, the drawback and conundrum of immunoassay are the unceasing problem in standardization of quality of antibodies and time/ effort for the intensive production. Therefore, there is an urgent need for the development of a standardized assay to detect gastric cancer at the early stage. Aptamers are DNA or RNA oligonucleotides with structural domain which recognize ligands such as proteins with superior affinity and specificity when compared to antibodies. In this study, SELEX (Systematic Evolution of Ligands by Exponential enrichment) technique was adopted to screen a random 30mer RNA library for aptamers targeting CEA, CA50 and CA72-4 respectively. Combined with high-throughput sequencing, we identified 6 aptamers which specifically target for these three biomarkers of gastrointestinal cancer. Intriguingly, the predicted secondary structures of RNA aptamers from each antigen showed significant structural similarity, suggesting the structural recognition between the aptamers and the antigens. Moreover, we determined the dissociation constants of all the aptamers to their corresponding antigens by fluorescence spectroscopy, which further demonstrated high affinities between the aptamers and the antigens. In addition, immunostaining of gastric adenocarcinoma cell line AGS using CEA Aptamer probe showed positive fluorescent signal which proves the potential of the aptamer as a detection tool for gastric cancer. Furthermore, substantially decreased cell viability and growth were observed when human colorectal cell line LS-174T was transfected with each individual aptamers. Taking together, these novel RNA aptamers targeting gastrointestinal cancer biomarker CEA, CA50 and CA72-4 will aid further development and standardization of clinical diagnostic method with better sensitivity and specificity, and potentially future therapeutics development of gastric cancer.-
dc.languageeng-
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action-
dc.relation.ispartofPLoS One-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAGS cell line-
dc.subjectbinding affinity-
dc.subjectcell growth-
dc.subjectcell viability-
dc.subjectcontrolled study-
dc.titleNovel RNA aptamers targeting gastrointestinal cancer biomarkers CEA, CA50 and CA72-4 with superior affinity and specificity-
dc.typeArticle-
dc.identifier.emailYung, MMH: mhyung@hku.hk-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0198980-
dc.identifier.pmid30303958-
dc.identifier.scopuseid_2-s2.0-85054756411-
dc.identifier.hkuros301796-
dc.identifier.volume13-
dc.identifier.issue10-
dc.identifier.spagearticle no. e0198980-
dc.identifier.epagearticle no. e0198980-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats