Anticancer Activity of the PR Domain of Tumor Suppressor RIZ1

Sun, Wanpeng; Liao, Qiao; Liu, Qiang; Chen, Lifeng; Ling, Binbing; Sammynaiken, Ramaswami; Yang, Jian

doi:10.7150/ijms.8.161

Cited by 15 publications

(16 citation statements)

References 30 publications

(36 reference statements)

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“…RIZ-PR has tumor suppressor activity whereas RIZ-CR has been described to acts as an oncogene. 34,35 The probe used in our gene expression profiling analyses did not distinguish between the two transcripts. However, in the RT-qPCR validation of the expression levels, we analyzed the gene expression of each transcript and found that both the tumor-suppressive RIZ-PR and the oncogenic RIZ-CR were up-regulated.…”

Section: Discussionmentioning

confidence: 99%

t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients

et al. 2014

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IntroductionThe t(6;9)(p22;q34), frequently reported with a breakpoint in 6p23 but now known to involve the DEK gene mapping to 6p22.3, is a rare translocation, estimated to occur in 1-2% of cases of childhood acute myeloid leukemia (AML). 1 The translocation was first identified in 1976, and the first pediatric patient was described in 1982.2,3 The World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia from 2008 listed the t(6;9)(p22;q34) as a distinct entity. 4 However, our current knowledge of t(6;9)(p22;q34) in AML is drawn from relatively small series of patients, predominantly adults, associating t(6;9) with young age at onset and a poor outcome. 1,[5][6][7] Typically, the t(6;9) presents as de novo AML, morphologically associated with FrenchAmerican-British (FAB) type M2, bone marrow basophilia, Auer rods, and dysplasia. 1,5,7,8 The translocation is primarily the sole cytogenetic abnormality (80%); among the 20% of ©2014 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol.2013 The online version of this article has a Supplementary Appendix. Manuscript received on September 24, 2013. Manuscript accepted on January 13, 2014 Acute myeloid leukemia with t(6;9)(p22;q34) is listed as a distinct entity in the 2008 World Health Organization classification, but little is known about the clinical implications of t(6;9)-positive myeloid leukemia in children. This international multicenter study presents the clinical and genetic characteristics of 62 pediatric patients with t(6;9)/DEK-NUP214-rearranged myeloid leukemia; 54 diagnosed as having acute myeloid leukemia, representing <1% of all childhood acute myeloid leukemia, and eight as having myelodysplastic syndrome. The t(6;9)/DEK-NUP214 was associated with relatively late onset (median age 10.4 years), male predominance (sex ratio 1.7), French-AmericanBritish M2 classification (54%), myelodysplasia (100%), and FLT3-ITD (42%). Outcome was substantially better than previously reported with a 5-year event-free survival of 32%, 5-year overall survival of 53%, and a 5-year cumulative incidence of relapse of 57%. Hematopoietic stem cell transplantation in first complete remission improved the 5-year event-free survival compared with chemotherapy alone (68% versus 18%; P<0.01) but not the overall survival (68% versus 54%; P=0.48). The presence of FLT3-ITD had a non-significant negative effect on 5-year overall survival compared with non-mutated cases (22% versus 62%; P=0.13). Gene expression profiling showed a unique signature characterized by significantly higher expression of EYA3, SESN1, PRDM2/RIZ, and HIST2H4 genes. In conclusion, t(6;9)/DEK-NUP214 represents a unique subtype of acute myeloid leukemia with a high risk of relapse, high frequency of FLT3-ITD, and a specific gene expression signature. t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients

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Section: Discussionmentioning

confidence: 99%

t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients

et al. 2014

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“…The increase in RIZ1 mRNA expression has been reported at late stage of several cancers (Pastural et al, 2007;Sun et al, 2011). This may be due to the non-specific reaction of RIZ1 RT-PCR primers targeting PR domain which also bind to isoform d and MTB-ZF.…”

Section: Discussionmentioning

confidence: 97%

Contribution of RIZ1 to Regulation of Proliferation and Migration of a Liver Fluke-Related Cholangiocarcinoma Cell

Khaenam

Niibori²,

Okada³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Purpose: Retinoblastoma-interacting zinc finger gene (RIZ1) is a tumor suppressor gene which is highly inactivated by promoter hypermethylation in patients with liver fluke-related cholangiocarcinoma (CCA). Epigenetic aberration of this gene might withdraw the ability to restrain tumor cell proliferation and migration. We aimed to define the role of RIZ1 on cell proliferation and migration in CCA cell line. Materials and methods: Small interference RNA (siRNA) was used to knock down the expression of RIZ1 in a CCA-derived cell line in which cell proliferation and cell migration were performed. Results: A predominant nuclear localization of RIZ1 was observed. Reduction of RIZ1 by siRNA augmented cell proliferation and migration. Conclusion: The result suggested that RIZ1 might play a role in regulating cell proliferation and migration in CCA. Reduction of RIZ1 expression may aggravate the progression of CCA.

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“…The PR domain of PRDM2/RIZ1 itself showed growth inhibitory and anticancer activities; indeed, it increased cell death when transfected in human hepatoma HuH7 cells [81]. Likewise, it inhibited cell proliferation and induced apoptosis in cultured primary meningioma cells and limited xenograft high-grade meningiomas tumor growth in nude mice through its methyltransferase activity [82].…”

Section: Prdm2mentioning

confidence: 99%

Multifaceted Role of PRDM Proteins in Human Cancer

Casamassimi

Rienzo

Zazzo

et al. 2020

IJMS

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The PR/SET domain family (PRDM) comprise a family of genes whose protein products share a conserved N-terminal PR [PRDI-BF1 (positive regulatory domain I-binding factor 1) and RIZ1 (retinoblastoma protein-interacting zinc finger gene 1)] homologous domain structurally and functionally similar to the catalytic SET [Su(var)3-9, enhancer-of-zeste and trithorax] domain of histone methyltransferases (HMTs). These genes are involved in epigenetic regulation of gene expression through their intrinsic HMTase activity or via interactions with other chromatin modifying enzymes. In this way they control a broad spectrum of biological processes, including proliferation and differentiation control, cell cycle progression, and maintenance of immune cell homeostasis. In cancer, tumor-specific dysfunctions of PRDM genes alter their expression by genetic and/or epigenetic modifications. A common characteristic of most PRDM genes is to encode for two main molecular variants with or without the PR domain. They are generated by either alternative splicing or alternative use of different promoters and play opposite roles, particularly in cancer where their imbalance can be often observed. In this scenario, PRDM proteins are involved in cancer onset, invasion, and metastasis and their altered expression is related to poor prognosis and clinical outcome. These functions strongly suggest their potential use in cancer management as diagnostic or prognostic tools and as new targets of therapeutic intervention.

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Anticancer Activity of the PR Domain of Tumor Suppressor RIZ1

Cited by 15 publications

References 30 publications

t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients

t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients

Contribution of RIZ1 to Regulation of Proliferation and Migration of a Liver Fluke-Related Cholangiocarcinoma Cell

Multifaceted Role of PRDM Proteins in Human Cancer

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