Downregulated PIRH2 Can Decrease the Proliferation of Breast Cancer Cells

Yang, Shuyun; Chen, Yingying; Sun, Fulan; Ni, Qing; Wang, Hua; Huang, Yeqing; Zhang, Chunhui; K, Liu; Wang, Shuo; Qiu, Jian; Xu, Zhen; Lu, Hua; He, Zhiqiang

doi:10.1016/j.arcmed.2016.06.004

Cited by 9 publications

(7 citation statements)

References 19 publications

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“…STEAP3-mediated downstream responsed to p53, including promoting apoptosis [ 35 , 36 ]. PIRH2-mediated E3-dependent ubiquitination and proteasomal degradation of target proteins, including tumor protein 53, histone deacetylase 1, and cyclin-dependent kinase inhibitor 1B, thus regulating their levels and cell cycle progression [ 37–39 ]. We also performed Gene Ontology (GO) analysis to survey the biological processes ( Figure 6 B).…”

Section: Resultsmentioning

confidence: 99%

Imsnc761 and DDX6 synergistically suppress cell proliferation and promote apoptosis via p53 in testicular embryonal carcinoma cells

et al. 2018

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Intermediate-sized non-coding RNAs (imsncRNAs) have been shown to play important regulatory roles in the development of several eukaryotic organisms. In the present research, we selected imsncRNA 761 (imsnc761) as a research target. Expression analyses in a previous study showed that imsnc761 was down-regulated in maturation-arrested testis tissues as compared with the level in normal controls. In the present study, we found that imsnc761 could interact with DEAD-box helicase 6 (DDX6) to induce NTERA-2 (NT2 (testicular embryonal carcinoma cell)) cell apoptosis and proliferation inhibition via the p53 pathway. This interaction between imsnc761 and DDX6 also inhibited mitochondrial function and specific gene transcription and translation. To facilitate further research, we used label-free quantitation method to analyze the associated differences in Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways and biological processes. This confirmed the changes in several specific pathways, which matched our molecular experimental results.

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Section: Resultsmentioning

confidence: 99%

Imsnc761 and DDX6 synergistically suppress cell proliferation and promote apoptosis via p53 in testicular embryonal carcinoma cells

et al. 2018

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“…Human Pirh2 (p53-induced RING-H2 protein) is encoded by the RCHY1 gene. Decrease of Pirh2 expression in the breast cancer cells result in reduced tumor cell growth via the inhibition of cell proliferation and the interruption of cell cycle transition [ 58 ]. It is suggested that TFAP2C overexpression correlates with poor overall survival after 10 years of diagnosis of breast cancer [ 59 ].…”

Section: Resultsmentioning

confidence: 99%

Graph-theoretical comparison of normal and tumor networks in identifying BRCA genes

Dopazo

Erten

2017

BMC Syst Biol

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BackgroundIdentification of driver genes related to certain types of cancer is an important research topic. Several systems biology approaches have been suggested, in particular for the identification of breast cancer (BRCA) related genes. Such approaches usually rely on differential gene expression and/or mutational landscape data. In some cases interaction network data is also integrated to identify cancer-related modules computationally.ResultsWe provide a framework for the comparative graph-theoretical analysis of networks integrating the relevant gene expression, mutations, and potein-protein interaction network data. The comparisons involve a graph-theoretical analysis of normal and tumor network pairs across all instances of a given set of breast cancer samples. The network measures under consideration are based on appropriate formulations of various centrality measures: betweenness, clustering coefficients, degree centrality, random walk distances, graph-theoretical distances, and Jaccard index centrality.ConclusionsAmong all the studied centrality-based graph-theoretical properties, we show that a betweenness-based measure differentiates BRCA genes across all normal versus tumor network pairs, than the rest of the popular centrality-based measures. The AUROC and AUPR values of the gene lists ordered with respect to the measures under study as compared to NCBI BioSystems pathway and the COSMIC database of cancer genes are the largest with the betweenness-based differentiation, followed by the measure based on degree centrality. In order to test the robustness of the suggested measures in prioritizing cancer genes, we further tested the two most promising measures, those based on betweenness and degree centralities, on randomly rewired networks. We show that both measures are quite resilient to noise in the input interaction network. We also compared the same measures against a state-of-the-art alternative disease gene prioritization method, MUFFFINN. We show that both our graph-theoretical measures outperform MUFFINN prioritizations in terms of ROC and precions/recall analysis. Finally, we filter the ordered list of the best measure, the betweenness-based differentiation, via a maximum-weight independent set formulation and investigate the top 50 genes in regards to literature verification. We show that almost all genes in the list are verified by the breast cancer literature and three genes are presented as novel genes that may potentialy be BRCA-related but missing in literature.

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“…Previous studies have demonstrated the role of Pirh2 as a tumor suppressor and prognostic marker in various human cancer subtypes (Hakem et al, 2011 , Halaby et al, 2013 ). However, human Pirh2 also has been reported to be overexpressed in cancers, such as breast cancer, and was found to be highly associated with tumor grade, size, and Ki-67 expression (Yang et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have shown that Pirh2 regulates cellular homeostasis in both p53-dependent and p53-independent cellular contexts. Moreover, based on its substrates, the association of Pirh2 with the occurrence and prognosis of malignant tumors has been confirmed (Jung et al, 2012 , Daks et al, 2016 , Yang et al, 2016 ). Pirh2 ubiquitinates substrate proteins and directs them through degradation pathways involved in apoptosis induction, cell cycle regulation, and DNA repair.…”

Section: Introductionmentioning

confidence: 96%

Pirh2 mediates the sensitivity of myeloma cells to bortezomib via canonical NF-κB signaling pathway

et al. 2018

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Clinical success of the proteasome inhibitor established bortezomib as one of the most effective drugs in treatment of multiple myeloma (MM). While survival benefit of bortezomib generated new treatment strategies, the primary and secondary resistance of MM cells to bortezomib remains a clinical concern. This study aimed to highlight the role of p53-induced RING-H2 (Pirh2) in the acquisition of bortezomib resistance in MM and to clarify the function and mechanism of action of Pirh2 in MM cell growth and resistance, thereby providing the basis for new therapeutic targets for MM. The proteasome inhibitor bortezomib has been established as one of the most effective drugs for treating MM. We demonstrated that bortezomib resistance in MM cells resulted from a reduction in Pirh2 protein levels. Pirh2 overexpression overcame bortezomib resistance and restored the sensitivity of myeloma cells to bortezomib, while a reduction in Pirh2 levels was correlated with bortezomib resistance. The levels of nuclear factor-kappaB (NF-κB) p65, pp65, pIKBa, and IKKa were higher in bortezomib-resistant cells than those in parental cells. Pirh2 overexpression reduced the levels of pIKBa and IKKa, while the knockdown of Pirh2 via short hairpin RNAs increased the expression of NF-κB p65, pIKBa, and IKKa. Therefore, Pirh2 suppressed the canonical NF-κB signaling pathway by inhibiting the phosphorylation and subsequent degradation of IKBa to overcome acquired bortezomib resistance in MM cells.

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Downregulated PIRH2 Can Decrease the Proliferation of Breast Cancer Cells

Cited by 9 publications

References 19 publications

Imsnc761 and DDX6 synergistically suppress cell proliferation and promote apoptosis via p53 in testicular embryonal carcinoma cells

Imsnc761 and DDX6 synergistically suppress cell proliferation and promote apoptosis via p53 in testicular embryonal carcinoma cells

Graph-theoretical comparison of normal and tumor networks in identifying BRCA genes

Pirh2 mediates the sensitivity of myeloma cells to bortezomib via canonical NF-κB signaling pathway

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