Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/91180
DC FieldValueLanguage
dc.contributorChinese Mainland Affairs Officeen_US
dc.contributorDepartment of Applied Biology and Chemical Technologyen_US
dc.creatorLo, LHen_US
dc.creatorLam, CYen_US
dc.creatorTo, JCen_US
dc.creatorChiu, CHen_US
dc.creatorKeng, VWen_US
dc.date.accessioned2021-09-10T05:51:22Z-
dc.date.available2021-09-10T05:51:22Z-
dc.identifier.issn0006-291Xen_US
dc.identifier.urihttp://hdl.handle.net/10397/91180-
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.rights©2021 Elsevier Inc. All rights reserved.en_US
dc.subjectHepatocellular carcinomaen_US
dc.subjectSleeping Beautyen_US
dc.subjectForward genetic screenen_US
dc.subjectCNPY2en_US
dc.subjectACTN2en_US
dc.subjectMetastasisen_US
dc.titleSleeping Beauty insertional mutagenesis screen identifies the pro-metastatic roles of CNPY2 and ACTN2 in hepatocellular carcinoma tumor progressionen_US
dc.typeJournal/Magazine Articleen_US
dc.identifier.spage70en_US
dc.identifier.epage77en_US
dc.identifier.volume541en_US
dc.identifier.doi10.1016/j.bbrc.2021.01.017en_US
dcterms.abstractA forward genetic Sleeping Beauty (SB) insertional mutagenesis screen, followed by high-throughput transcriptome sequencing, was used to identify driver genes responsible for hepatocellular carcinoma (HCC)-associated metastasis. Using RNA-sequencing (RNA-seq) to identify transposon-endogenous transcriptome fusion genes, the phylogenetic lineage between the parental liver tumor and secondary metastasis can be determined to provide mechanistic insight to genetic changes involved in the metastatic evolution process. In the current study, two novel candidate genes were identified to be potentially involved in HCC-associated metastatic progression, canopy FGF signaling regulator 2 (Cnpy2) and actinin alpha 2 (Actn2). Transposon-Cnpy2 fusion transcripts were identified in both primary liver tumors and lung metastases. Its significant association with clinicopathological characteristics and correlated gene enrichment in metastasis-related mechanisms suggest its potential role in modulating local invasion and angiogenesis. Other known driver genes for human HCC that can also promote metastatic progression include epidermal growth factor receptor (Egfr) and RNA imprinted and accumulated in nucleus (Rian). Metabolic pathway related gene carbamoyl phosphate synthetase (Cps1) was identified to play an important role in early HCC development, while cell junction-related pathway gene Rac family small GTPase 1 (Rac1) was identified to take part in both HCC and pro-metastatic progression. Importantly, actinin alpha 2 (Actn2) was identified exclusively in the secondary metastasis site and its role in HCC-related metastatic process was elucidated using in vitro approaches. ACTN2-overexpression in human liver cancer cells displayed enhanced cellular motility and invasion abilities, indicating its possible function in later stage of metastasis, such as extravasation and lung colonization.en_US
dcterms.accessRightsopen accessen_US
dcterms.bibliographicCitationBiochemical and biophysical research communications, 19 Feb. 2021, v. 541, p. 70-77en_US
dcterms.isPartOfBiochemical and biophysical research communicationsen_US
dcterms.issued2021-02-19-
dc.identifier.isiWOS:000615714500011-
dc.identifier.pmid33482578-
dc.identifier.eissn1090-2104en_US
dc.description.validate202109 bcrcen_US
dc.description.oaAuthor’s Originalen_US
dc.identifier.FolderNumbera0613-n06-
dc.identifier.SubFormID597-
dc.description.fundingSourceRGCen_US
dc.description.fundingTextR5050-18en_US
dc.description.pubStatusPublisheden_US
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