ShRNA-Targeted Centromere Protein A Inhibits Hepatocellular Carcinoma Growth

Li, Yongmei; Zhu, Zhi; Zhang, Shu‐Hui; Yu, Danghui; Yu, Hong‐Yu; Liu, Lina; Cao, Xiao-zhe; Wang, Li; Gao, Hengjun; Zhu, Min

doi:10.1371/journal.pone.0017794

Cited by 117 publications

(128 citation statements)

References 51 publications

(53 reference statements)

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“…This supports the hypothesis that deleted forms of HBx may contribute to liver carcinogenesis (13,(30)(31)(32). Our previous findings also demonstrated that CENP-A overexpression was correlated with serum HBsAg states in HCC patients (16). In this study, we identified a positive correlation between the expression of CENP-A immuno reactivity and the HBx COOH mutation in HCC tissues.…”

Section: Discussionsupporting

confidence: 89%

“…The primary antibodies included anti-CENP-A (ab13939, 1:100, Abcam, Cambridge, UK), and anti-Hepatitis B virus X antigen (HBxAg, ab235, Abcam; 1:500). We defined that a <10% represented low, and >10% represented high levels of CENP-A expression (16).…”

Section: Methodsmentioning

confidence: 99%

“…RT-PCR and qPCR analysis were performed as previously described (16,20). Total RNA was extracted from cells or tissues with an RNeasy mini kit (Qiagen, Germany) according to the manufacturer's protocol.…”

Section: Rna Isolation Reverse Transcription-polymerase Chain Reactimentioning

confidence: 99%

“…The anticancer effects of CENP-A depletion are likely mediated by a large number of genes involved in cell cycle control and apoptosis, including CHK2, P21waf1, P27 Kip1, SKP2, MDM2, Bcl-2, and Bax (14,15). Furthermore, CENP-A over expression was correlated with serum HBsAg states, tumor histological grade and P53 immunopositivity (16). In the present study, we aimed to investigate the relationship between CENP-A and HBx protein in HCC.…”

Section: Introductionmentioning

confidence: 99%

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Hepatitis B virus X protein mutant upregulates CENP-A expression in hepatoma cells

Liu

Li²,

Zhang³

et al. 2011

Oncol Rep

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Abstract. The carcinogenic role of hepatitis B virus x protein (HBx) in hepatocellular carcinoma (HCC) remains largely unknown. Centromere protein A (CENP-A) has been found to be frequently overexpressed in HCC. In the present study, we aimed to investigate the role of HBx in regulating CENP-A activity in HCC carcinogenesis. CENP-A expression was examined and the HBx gene was sequenced in 20 HBsAgpositive HCC patients and corresponding non-cancerous liver tissues. The influence of HBx mutants on CENP-A expression in HepG2 cells was analyzed by a series of assays. We found that CENP-A expression was significantly elevated in HCC tissues. HBx deletion, especially the COOH-terminal deletion of HBx is a frequent event in HBV-associated HCC tissues. A positive correlation was found between CENP-A expression and HBx COOH mutation in HCC tissues. HBx mutant increased the expression of the CENP-A mRNA and protein compared with full-length HBx. However, HBx did not directly interact with CENP-A. It is concluded that overexpression of CENP-A is closely associated with HBx COOH mutation in HCC. HBx mutant can increase CENP-A expression, probably through a mechanism independent of their physical combination, and thereby it may represent a potential therapeutic strategy for HCC.

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Section: Discussionsupporting

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Section: Rna Isolation Reverse Transcription-polymerase Chain Reactimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hepatitis B virus X protein mutant upregulates CENP-A expression in hepatoma cells

Liu

Li²,

Zhang³

et al. 2011

Oncol Rep

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“…Son çalışmalar ayrıca CENP-A'nın DNA'nın hasarlı bölgelerinde toplandığını ve çift iplik DNA kırık tamirinde yer alabileceğini düşündürmektedir. 27 CENP-A düzeyleri östrojen reseptör (ER) negatiflerde ER-pozitiflere göre yüksek bulunmuştur. Çalışmada CENP-B düzeyleri ER-pozitif ve ER-negatif tümörler arasında karşılaştırılmış, ER-pozitif ve ER-negatif tümörler arasında CENP-B düzeyin-de farklılık gözlenmemiştir.…”

Section: şEkil 41 Cenp-a Geninin 2p233 Kromozomal Lokalizasyonuunclassified

Protein expression changes in breast cancer and their importance

Sevimli¹

2013

Dicle Med J

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Studies about nucleic acids have increased after the publication of DNA's three dimensional structure by Watson and Crick. Nucleic acids are the heritable molecules which contain codes for proteins. Proteins are the most important elements in molecular world because they are the basic structural and functional components of a living organism. Clarifying the celluler events that involve proteins are important in many areas for example diagnosis and treatment determination of diseases or development of new drugs. Proteome that comes from a combination of the terms protein and genome, is one of the important field in these days. The studies in this area have accelerated and gained a different place especially with after the completion of human genome project. In synthesis of a protein just only genetic information is not enough. At the same time the change or changes of a protein after the synthesis, the final version and transporting to final localization of it also important. Because having defects in mailing cells of breast cancer, the first targets of treatment must be proteins. In this way the studies on proteins are important to determine prognostic and diagnostic disease markers and also significant for identifying new treatment strategies.Key words: Genom, proteom, breast cancer ÖZET Nükleik asitlerle ilgili çalışmalar, Watson ve Crick'in DNA'nın üç boyutlu yapısını yayınladıktan sonra artmış-tır. Nükleik asitler kalıtsal moleküllerdir ve proteinlere ait şifreleri taşıyan moleküllerdir. Proteinler; canlı materyalin yapı ve işlevinde temel olan, moleküler dünyanın en önemli elemanlarındandır. Proteinlerin yer aldığı hücresel olayların aydınlatılması da birçok alanda önem taşımak-tadır. Hastalıkların tanısı, tedavilerin belirlenmesi ve yeni ilaçların geliştirilebilmesi bu açıdan oldukça önemlidir. Proteom, protein ve genom terimlerinin birleşimi olup; son zamanlarda üzerinde durulan önemli çalışma alanlarından biridir. Bu alandaki çalışmalar özellikle insan genom projesinin tamamlanmasıyla hız kazanmış, bu projeden elde edilen bilgilerle farklı bir boyut kazanmıştır. Bir proteinin sentezlenmesinde sadece genetik bilgi yeterli değildir. Aynı zamanda protein sentezlendikten sonra, kendine uygun son halini kazanmak için değişim veya değişimlere uğrayarak son halini almasında ve hücrede görev yapacağı yere taşınmasında önem taşımaktadır. Meme kanserindeki malign hücrelerde defektler olduğun-dan, tedavisinde ilk hedef proteinlerdir. Bu nedenle bu ça-lışmalar, diyagnostik ve prognostik hastalık belirteçlerinin tanımlanmasına ve yeni tedavi stratejilerinin belirlenmesini sağlayabilir.Anahtar kelimeler: Genom, proteom, meme kanseri GİRİŞ Kadınlarda en sık rastlanan kanser, meme kanseridir. Tanı ve tedavide yeni gelişmelerin artmasına rağmen, günümüzde hala önemli bir morbidite ve mortalite nedenidir.

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SiRNA‐targeted carboxypeptidase D inhibits hepatocellular carcinoma growth

Jin

Feng

et al. 2013

Cell Biology International

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Carboxypeptidase D (CPD), a membrane-bound metallocarboxypeptidase that functions as a docking receptor for duck hepatitis B virus, is frequently overexpressed in human cancers. We have explored its expression pattern, clinical significance, and biological function of CPD in hepatocellular carcinoma (HCC). CPD expression was markedly elevated in HCCs relative to adjacent non-tumor liver tissues, as determined by quantitative real-time polymerase chain reaction and Western blot analysis. Immunohistochemistry showed that 164 of 400 (41%) HCCs had high expression of CPD. CPD overexpression was significantly associated with serum levels of hepatitis B surface antigen and hepatitis B e antigen, liver cirrhosis, pathological grade, and intrahepatic metastasis. Knockdown of endogenous CPD expression in Huh7 HCC cells by RNA interference reduced cell proliferation, blocked the cell cycle at G1 phase, and increased apoptosis. Many genes implicated in cell-cycle regulation, including P21waf1, P27 Kip1, SKP2, and CDC2, were deregulated by CPD downregulation. Thus CPD is frequently upregulated in HCC, and targeting CPD inhibits HCC cell proliferation through induction of G1 cell-cycle arrest and apoptosis, thereby providing a potential therapeutic target for this malignancy.

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ShRNA-Targeted Centromere Protein A Inhibits Hepatocellular Carcinoma Growth

Cited by 117 publications

References 51 publications

Hepatitis B virus X protein mutant upregulates CENP-A expression in hepatoma cells

Hepatitis B virus X protein mutant upregulates CENP-A expression in hepatoma cells

Protein expression changes in breast cancer and their importance

SiRNA‐targeted carboxypeptidase D inhibits hepatocellular carcinoma growth

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