ICBP90 belongs to a new family of proteins with an expression that is deregulated in cancer cells

Mousli, Marc; Hopfner, Raphaël; Abbady, Abdul Qader; Monté, Didier; Jeanblanc, Michaël; Oudet, P; Louis, B. Gregory; Bronner, Christian

doi:10.1038/sj.bjc.6601068

Cited by 131 publications

(162 citation statements)

References 27 publications

(36 reference statements)

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“…Although UHRF1 promoter bears a CpG island, no DNA methylation was found in normal or tumor tissue, excluding the possibility of an epigenetic expression feedback loop. As UHRF1 is a known E2F1 target, 29,45 we also examined E2F1 mRNA expression levels in this sample set. Indeed, a strong relationship was observed between the expression levels of the 2 genes, supporting the concept that UHRF1 regulation is under the control of the pRb/E2F1pathway.…”

Section: Discussionmentioning

confidence: 99%

UHRF1‐mediated tumor suppressor gene inactivation in nonsmall cell lung cancer

Daskalos

Oleksiewicz

Filia

et al. 2010

Cancer

107

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BACKGROUND:The UHRF1 gene possesses an essential role in DNA methylation maintenance, but its contribution to tumor suppressor gene hypermethylation in primary human cancers currently remains unclear. METHODS: mRNA expression levels of UHRF1, DNMT1, DNMT3A, DNMT3B, and E2F1 were evaluated in 105 primary nonsmall cell lung carcinomas by quantitative polymerase chain reaction. The methylation status of CDKN2A and RASSF1 promoters was examined by pyrosequencing. UHRF1 was knocked down by short hairpin RNA in A549 lung adenocarcinoma cells. RESULTS: All 4 genes were overexpressed in a coordinated manner in the lung tumor tissues, and their expression correlated with that of E2F1. Higher UHRF1 expression in tumor tissues correlated with the hypermethylation of CDKN2A (P ¼ .005) and RASSF1 promoters (P ¼ .034), and the relationship with a combined epigenotype was even stronger (P ¼ 2.3 Â 10 À4 ). When UHRF1 was knocked down in A549 lung adenocarcinoma cells, lower methylation levels of RASSF1, CYGB, and CDH13 promoters were observed. Also, UHRF1 knockdown clones demonstrated reduced proliferation and decreased cell migration properties. CONCLUSIONS: Our data demonstrate that UHRF1 is a key epigenetic switch, which controls cell cycle in nonsmall cell lung carcinoma through its ability to sustain the transcriptional silencing of tumor suppressor genes by maintaining their promoters in a hypermethylated status. Thus, UHRF1 should be considered, along with DNMTs, among the potential targets for cancer treatment and/or therapeutic stratification.

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Section: Discussionmentioning

confidence: 99%

UHRF1‐mediated tumor suppressor gene inactivation in nonsmall cell lung cancer

Daskalos

Oleksiewicz

Filia

et al. 2010

Cancer

107

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“…The consequences of this hypermethylation and its maintenance are not clearly understood but they likely target the expression of specific genes involved in the DNA damage response. We hypothesized that UHRF1 (Ubiquitin-like, containing PHD and RING Finger domains, 1) could be a major effector of the p73 deregulation, since this nuclear protein is known to be over-expressed in numerous cancer cell lines and tissues [8][9][10][11]. 4 Several studies have shown that UHRF1 participates in the control of cell proliferation and cell cycle transition from G1 to S, by regulating the expression of several genes, including RB1 and p16 INK4A [12,13].…”

Section: Introductionmentioning

confidence: 99%

“…There are several lines of evidence that UHRF1 deregulation may impair the control of G1/S transition during cell cycle checkpoint activation [8,9,14]. Since such activation is known to occur during the DNA damage-related apoptosis of TQ [23][24][25][26], we analyzed the expression levels of UHRF1 and its partners DNMT1 and HDAC1 in TQ-treated Jurkat cells.…”

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confidence: 99%

Induction of apoptosis by thymoquinone in lymphoblastic leukemia Jurkat cells is mediated by a p73-dependent pathway which targets the epigenetic integrator UHRF1

Alhosin

Abusnina

Achour

et al. 2010

Biochemical Pharmacology

130

116

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The salvage anti-tumoral pathway which implicates the p53-related p73 gene is not yet fully characterized. We therefore attempted to identify the up-and down-stream events involved in the activation of the p73-dependent pro-apoptotic pathway, by focusing on the anti-apoptotic and epigenetic integrator UHRF1 which is essential for cell cycle progression. For this purpose, we analyzed the effects of a known anti-neoplastic drug, thymoquinone (TQ), on the p53-deficient acute lymphoblastic leukemia (ALL) Jurkat cell line. Our results showed that TQ inhibits the proliferation of Jurkat cells and induces G1 cell cycle arrest in a dose-dependent manner. Moreover, TQ treatment triggers programmed cell death, production of reactive oxygen species (ROS) and alteration of the mitochondrial membrane potential (m). TQ-induced apoptosis, confirmed by the presence of hypodiploid G0/G1 cells, is associated with a rapid and sharp re-expression of p73 and dose-dependent changes of the levels of caspase-3 cleaved subunits. These modifications are accompanied by a dramatic down-regulation of UHRF1 and two of its main partners, namely DNMT1 and HDAC1, which are all involved in the epigenetic code regulation. Knockdown of p73 expression restores UHRF1 expression, reactivates cell cycle progression and inhibits TQ-induced apoptosis. Altogether our results showed that TQ mediates its growth inhibitory effects on ALL p53-mutated cells via the activation of a p73-dependent mitochondrial and cell cycle checkpoint signaling pathway which subsequently targets UHRF1.

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“…The tumour suppressor p53, which is deficient in 50% of all human cancers (Hussain and Harris, 2000), indirectly downregulates UHRF1 through the upregulation of p21/WAF1 and subsequent deactivation of E2F1 (Arima et al, 2004). Expression of UHRF1 is upregulated in various cancers, including breast, prostate, lung, astrocytomas, pancreatic cancers, and cervical cancer (Mousli et al, 2003;Unoki et al, 2004;Crnogorac-Jurcevic et al, 2005;Jenkins et al, 2005;Lorenzato et al, 2005;Oba-Shinjo et al, 2005). Overexpression of UHRF1 in these cancers may be partially due to the inactivation of p53, although there are most probably several pathways which regulate UHRF1.…”

mentioning

confidence: 99%

“…The UHRF1 recruits DNA methyltransferase 1 (DNMT1) to the site with proliferating cell nuclear antigen (PCNA) and methylates the newly synthesised strands (Sharif et al, 2007;Achour et al, 2008). The UHRF1 promotes G1/S transition (Arima et al, 2004;Jeanblanc et al, 2005) and is a direct target of E2F transcription factor 1 (E2F1) (Mousli et al, 2003;Unoki et al, 2004;Abbady et al, 2005). The tumour suppressor p53, which is deficient in 50% of all human cancers (Hussain and Harris, 2000), indirectly downregulates UHRF1 through the upregulation of p21/WAF1 and subsequent deactivation of E2F1 (Arima et al, 2004).…”

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confidence: 99%

UHRF1 is a novel molecular marker for diagnosis and the prognosis of bladder cancer

et al. 2009

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BACKGROUND: Bladder cancer is the second most common cancer of the urinary system. Early diagnosis of this tumour and estimation of risk of future progression after initial transuretherial resection have a significant impact on prognosis. Although there are several molecular markers for the diagnosis and prognosis for this tumour, their accuracy is not ideal. Previous reports have shown that UHRF1 (ubiquitin-like with PHD and ring-finger domains 1) is essential for cellular proliferation. In this study, we examined whether UHRF1 can be a novel molecular marker of bladder cancer. METHODS: We performed real-time TaqMan quantitative reverse transcription -PCR and immunohistochemistry to examine expression levels of UHRF1 in bladder and kidney cancers. RESULTS: Significant overexpression of UHRF1 was observed in bladder cancer. The overexpression was correlated with the stage and grade of the cancer. Although UHRF1 expression in muscle-invasive cancer was greater than in non-invasive (pTa) or superficially invasive (pT1) cancers, UHRF1 could still be detected by immunohistochemistry in these early-stage cancers. Overexpression of UHRF1 in bladder cancer was associated with increased risk of progression after transurethral resection. High expression of UHRF1 in kidney cancer was also observed. But the increased levels of UHRF1 in kidney cancer were less significant compared with those in bladder cancer. CONCLUSION: Our result indicates that an immunohistochemistry-based UHRF1 detection in urine sediment or surgical specimens can be a sensitive and cancer-specific diagnostic and/or prognosis method, and may greatly improve the current diagnosis based on cytology.

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ICBP90 belongs to a new family of proteins with an expression that is deregulated in cancer cells

Cited by 131 publications

References 27 publications

UHRF1‐mediated tumor suppressor gene inactivation in nonsmall cell lung cancer

UHRF1‐mediated tumor suppressor gene inactivation in nonsmall cell lung cancer

Induction of apoptosis by thymoquinone in lymphoblastic leukemia Jurkat cells is mediated by a p73-dependent pathway which targets the epigenetic integrator UHRF1

UHRF1 is a novel molecular marker for diagnosis and the prognosis of bladder cancer

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