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Article: PDSS2‐Del2, a new variant of PDSS2, promotes tumor cell metastasis and angiogenesis in hepatocellular carcinoma via activating NF‐κB

TitlePDSS2‐Del2, a new variant of PDSS2, promotes tumor cell metastasis and angiogenesis in hepatocellular carcinoma via activating NF‐κB
Authors
Keywordsangiogenesis
dimethyl fumarate
hepatocellular carcinoma
metastasis
nuclear factor-κB
Issue Date2020
PublisherJohn Wiley & Sons Ltd, published in association with Federation of European Biochemical Societies. The Journal's web site is located at https://febs.onlinelibrary.wiley.com/journal/18780261
Citation
Molecular Oncology, 2020, v. 14 n. 12, p. 3184-3197 How to Cite?
AbstractHepatocellular carcinoma (HCC) is among the leading causes of cancer-related mortality worldwide. Our previous study identified a novel alternative splicing variant of prenyl diphosphate synthase subunit 2 (PDSS2) in HCC characterized by a deletion of exon 2, named PDSS2-Del2, which is devoid of the tumor-suppressive function of full-length PDSS2 (PDSS2-FL). To better understand the clinical significance of PDSS2-Del2, we performed a BaseScope™ assay on an HCC tissue microarray and found that positive staining for PDSS2-Del2 predicted a worse overall survival in patients with HCC (P = 0.02). PDSS2-Del2 levels correlated significantly with microvessel counts in HCC tumor tissues. Importantly, PDSS2-Del2 overexpression functionally promoted HCC metastasis, as demonstrated by in vitro and in vivo migration assays. In vivo assays also demonstrated that PDSS2-Del2 increased angiogenesis in xenografts. Furthermore, we discovered that elevated PDSS2-Del2 expression in HCC tumor cells decreased fumarate levels and activated the canonical nuclear factor-κB pathway. The epithelial-to-mesenchymal transition (EMT) and WNT/β-catenin signaling pathways were also activated by overexpression. Dimethyl fumarate (DMF), a fumaric acid ester, effectively reduced the metastasis induced by PDSS2-Del2 as observed with in vivo spleen-liver metastasis animal experiments. DMF is a prescribed oral therapy for multiple sclerosis and it might be a potential treatment for metastasis of patients with HCC. Early clinical trials are needed to validate its potential in this context.
Persistent Identifierhttp://hdl.handle.net/10722/300780
ISSN
2023 Impact Factor: 5.0
2023 SCImago Journal Rankings: 1.940
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZeng, T-
dc.contributor.authorTang, Z-
dc.contributor.authorLiang, L-
dc.contributor.authorSuo, D-
dc.contributor.authorLi, L-
dc.contributor.authorLi, J-
dc.contributor.authorYuan, Y-
dc.contributor.authorGuan, XY-
dc.contributor.authorLi, Y-
dc.date.accessioned2021-07-06T03:10:08Z-
dc.date.available2021-07-06T03:10:08Z-
dc.date.issued2020-
dc.identifier.citationMolecular Oncology, 2020, v. 14 n. 12, p. 3184-3197-
dc.identifier.issn1574-7891-
dc.identifier.urihttp://hdl.handle.net/10722/300780-
dc.description.abstractHepatocellular carcinoma (HCC) is among the leading causes of cancer-related mortality worldwide. Our previous study identified a novel alternative splicing variant of prenyl diphosphate synthase subunit 2 (PDSS2) in HCC characterized by a deletion of exon 2, named PDSS2-Del2, which is devoid of the tumor-suppressive function of full-length PDSS2 (PDSS2-FL). To better understand the clinical significance of PDSS2-Del2, we performed a BaseScope™ assay on an HCC tissue microarray and found that positive staining for PDSS2-Del2 predicted a worse overall survival in patients with HCC (P = 0.02). PDSS2-Del2 levels correlated significantly with microvessel counts in HCC tumor tissues. Importantly, PDSS2-Del2 overexpression functionally promoted HCC metastasis, as demonstrated by in vitro and in vivo migration assays. In vivo assays also demonstrated that PDSS2-Del2 increased angiogenesis in xenografts. Furthermore, we discovered that elevated PDSS2-Del2 expression in HCC tumor cells decreased fumarate levels and activated the canonical nuclear factor-κB pathway. The epithelial-to-mesenchymal transition (EMT) and WNT/β-catenin signaling pathways were also activated by overexpression. Dimethyl fumarate (DMF), a fumaric acid ester, effectively reduced the metastasis induced by PDSS2-Del2 as observed with in vivo spleen-liver metastasis animal experiments. DMF is a prescribed oral therapy for multiple sclerosis and it might be a potential treatment for metastasis of patients with HCC. Early clinical trials are needed to validate its potential in this context.-
dc.languageeng-
dc.publisherJohn Wiley & Sons Ltd, published in association with Federation of European Biochemical Societies. The Journal's web site is located at https://febs.onlinelibrary.wiley.com/journal/18780261-
dc.relation.ispartofMolecular Oncology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectangiogenesis-
dc.subjectdimethyl fumarate-
dc.subjecthepatocellular carcinoma-
dc.subjectmetastasis-
dc.subjectnuclear factor-κB-
dc.titlePDSS2‐Del2, a new variant of PDSS2, promotes tumor cell metastasis and angiogenesis in hepatocellular carcinoma via activating NF‐κB-
dc.typeArticle-
dc.identifier.emailLi, L: lilei728@HKUCC-COM.hku.hk-
dc.identifier.emailGuan, XY: xyguan@hku.hk-
dc.identifier.authorityGuan, XY=rp00454-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1002/1878-0261.12826-
dc.identifier.pmid33064899-
dc.identifier.pmcidPMC7718950-
dc.identifier.scopuseid_2-s2.0-85096759206-
dc.identifier.hkuros323262-
dc.identifier.volume14-
dc.identifier.issue12-
dc.identifier.spage3184-
dc.identifier.epage3197-
dc.identifier.isiWOS:000584663500001-
dc.publisher.placeUnited Kingdom-

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