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Conference Paper: RNAi-mediated PIN1 silencing inhibits HCC tumorigenicity

TitleRNAi-mediated PIN1 silencing inhibits HCC tumorigenicity
Authors
Issue Date2005
PublisherAmerican Association for Cancer Research.
Citation
The 96th Annual Meeting of the American Association for Cancer Research (AACR 2005), Anaheim, CA, 16-20 April 2005. In Cancer Research, 2005, v. 65 n. 9S, p. 1344, abstract no. 5718 How to Cite?
AbstractBackground The phospho-Ser/Thr-Pro specific prolyl-isomerase PIN1 has been implicated in multiple aspects of cell cycle regulation. Our previous findings showed that PIN1 was over-expressed in more than 50% of hepatocellular carcinoma (HCC), and its expression correlated significantly with β-catenin and cyclin D1 expression, suggesting the involvement of PIN1 in hepatocarinogenesis. This study aims to investigate whether inhibition of PIN1 expression would block cell proliferation and inhibit the transformed phenotype of HCC cells both in vitro and in vivo. Materials and Methods To examine the oncogenic role of PIN1 over-expression in HCC, siRNA eukaryotic expression vector of PIN1 and PIN1 cDNA under the control of a human CMV promoter were constructed and stably transfected into a HCC cell line - PLC/PRF/5 and a non-tumourigenic human liver cell line - MIHA, respectively. Tumourigenicity of siRNA stable PIN1 and PIN1 transfectants were determined by soft agar assay, colony formation assay and nude mice injection. The effect of PIN1 on cell growth was examined by MTT assay and flow cytometry analysis. cDNA microarray (Affymetrix array) analysis was employed to detect the differential gene expressions between PIN1 gene-silenced and vector controlled PLC/PRF/5 cell line. Results Using RNAi technology, we found that the expression of double-stranded RNA led to efficient and specific inhibition of endogenous PIN1 expression in PLC/PRF/5 cells as determined by RT-PCR and Western blotting, resulting in deregulated cell cycle progression and decreased proliferation by 57.6 ± 4.7%. Both colony formation and growth in soft agar were inhibited by PIN1 gene silencing. Conversely, stable expression of PIN1 in MIHA promoted cell transformation. Subcutaneous injection of PIN1 transfected MIHA cells into nude mice also conferred tumour formation whereas PIN1 gene silenced PLC/PRF/5 cells did not. By cDNA microarray analysis, several oncogenes including cyclin D1 and hnRNP A2 were significantly down-regulated by PIN1 gene silencing, suggesting an oncogenic role of PIN1 over-expression in hepatocarcinogenesis. Conclusion Our study suggests that PIN1 plays a functional role in the transformed phenotype of HCC cells and contributes to HCC carcinogenesis. PIN1 may therefore represent a potential target for HCC cancer therapy.
Persistent Identifierhttp://hdl.handle.net/10722/102899
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorPang, RWCen_HK
dc.contributor.authorLee, KWen_HK
dc.contributor.authorMan, Ken_HK
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorFan, STen_HK
dc.contributor.authorKwong, YLen_HK
dc.contributor.authorTse, EWCen_HK
dc.date.accessioned2010-09-25T20:49:22Z-
dc.date.available2010-09-25T20:49:22Z-
dc.date.issued2005en_HK
dc.identifier.citationThe 96th Annual Meeting of the American Association for Cancer Research (AACR 2005), Anaheim, CA, 16-20 April 2005. In Cancer Research, 2005, v. 65 n. 9S, p. 1344, abstract no. 5718-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/102899-
dc.description.abstractBackground The phospho-Ser/Thr-Pro specific prolyl-isomerase PIN1 has been implicated in multiple aspects of cell cycle regulation. Our previous findings showed that PIN1 was over-expressed in more than 50% of hepatocellular carcinoma (HCC), and its expression correlated significantly with β-catenin and cyclin D1 expression, suggesting the involvement of PIN1 in hepatocarinogenesis. This study aims to investigate whether inhibition of PIN1 expression would block cell proliferation and inhibit the transformed phenotype of HCC cells both in vitro and in vivo. Materials and Methods To examine the oncogenic role of PIN1 over-expression in HCC, siRNA eukaryotic expression vector of PIN1 and PIN1 cDNA under the control of a human CMV promoter were constructed and stably transfected into a HCC cell line - PLC/PRF/5 and a non-tumourigenic human liver cell line - MIHA, respectively. Tumourigenicity of siRNA stable PIN1 and PIN1 transfectants were determined by soft agar assay, colony formation assay and nude mice injection. The effect of PIN1 on cell growth was examined by MTT assay and flow cytometry analysis. cDNA microarray (Affymetrix array) analysis was employed to detect the differential gene expressions between PIN1 gene-silenced and vector controlled PLC/PRF/5 cell line. Results Using RNAi technology, we found that the expression of double-stranded RNA led to efficient and specific inhibition of endogenous PIN1 expression in PLC/PRF/5 cells as determined by RT-PCR and Western blotting, resulting in deregulated cell cycle progression and decreased proliferation by 57.6 ± 4.7%. Both colony formation and growth in soft agar were inhibited by PIN1 gene silencing. Conversely, stable expression of PIN1 in MIHA promoted cell transformation. Subcutaneous injection of PIN1 transfected MIHA cells into nude mice also conferred tumour formation whereas PIN1 gene silenced PLC/PRF/5 cells did not. By cDNA microarray analysis, several oncogenes including cyclin D1 and hnRNP A2 were significantly down-regulated by PIN1 gene silencing, suggesting an oncogenic role of PIN1 over-expression in hepatocarcinogenesis. Conclusion Our study suggests that PIN1 plays a functional role in the transformed phenotype of HCC cells and contributes to HCC carcinogenesis. PIN1 may therefore represent a potential target for HCC cancer therapy.-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research.-
dc.relation.ispartofCancer Researchen_HK
dc.titleRNAi-mediated PIN1 silencing inhibits HCC tumorigenicityen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailPang, RWC: robertap@hku.hken_HK
dc.identifier.emailLee, KW: tkwlee@hkucc.hku.hken_HK
dc.identifier.emailMan, K: kwanman@hkucc.hku.hken_HK
dc.identifier.emailPoon, RTP: poontp@hkucc.hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.emailKwong, YL: ylkwong@hku.hken_HK
dc.identifier.emailTse, EWC: ewctse@hku.hken_HK
dc.identifier.authorityLee, KW=rp00447en_HK
dc.identifier.authorityMan, K=rp00417en_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.identifier.authorityKwong, YL=rp00358en_HK
dc.identifier.authorityTse, EWC=rp00471en_HK
dc.identifier.hkuros99800en_HK
dc.identifier.volume65-
dc.identifier.issue9S-
dc.identifier.spage1344, abstract no. 5718-
dc.identifier.epage1344, abstract no. 5718-
dc.publisher.placeUnited States-

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