Inhibition of Recombining Binding Protein Suppressor of Hairless (RBPJ) Impairs the Growth of Prostate Cancer

Xue, Li; Li, Hecheng; Chen, Qi; Wang, Zhenlong; Zhang, Peng; Chen, Haiwen; Wang, Ziming; Chong, Tie

doi:10.1159/000430166

Cited by 11 publications

(8 citation statements)

References 46 publications

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“…Specifically, CSL silencing in MDA-MB-231 human breast cancer and DG75 Burkitt lymphoma cells enhanced tumor growth, with c-MYC-and NF-KB-dependent increases in cell survival. However, an opposite conclusion was suggested by other studies with cultured cancer cell lines, including one that was also with MDA-MB-231 cells (55)(56)(57). Thus, the possibility of distinct roles of NOTCH and CSL in specific cancer types needs further assessment in the context of their cells of origin and tumor microenvironment.…”

Section: Discussionmentioning

confidence: 83%

Notch-effector CSL promotes squamous cell carcinoma by repressing histone demethylase KDM6B

Labban¹,

Jo²,

Ostano³

et al. 2018

Journal of Clinical Investigation

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Section: Discussionmentioning

confidence: 83%

Notch-effector CSL promotes squamous cell carcinoma by repressing histone demethylase KDM6B

Labban¹,

Jo²,

Ostano³

et al. 2018

Journal of Clinical Investigation

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“…This gene displays frequent deletions or mutations in SCC4748. RBPJ encodes a transcriptional factor regulating Notch signaling pathway, which has been shown to be an effective therapeutic target in various tumours454950. By using this large sample size, we generated clinical background-related mutational signatures in ESCC.…”

Section: Discussionmentioning

confidence: 99%

Genomic analysis of oesophageal squamous-cell carcinoma identifies alcohol drinking-related mutation signature and genomic alterations

et al. 2017

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Approximately half of the world's 500,000 new oesophageal squamous-cell carcinoma (ESCC) cases each year occur in China. Here, we show whole-genome sequencing of DNA and RNA in 94 Chinese individuals with ESCC. We identify six mutational signatures (E1–E6), and Signature E4 is unique in ESCC linked to alcohol intake and genetic variants in alcohol-metabolizing enzymes. We discover significantly recurrent mutations in 20 protein-coding genes, 4 long non-coding RNAs and 10 untranslational regions. Functional analyses show six genes that have recurrent copy-number variants in three squamous-cell carcinomas (oesophageal, head and neck and lung) significantly promote cancer cell proliferation, migration and invasion. The most frequently affected genes by structural variation are LRP1B and TTC28. The aberrant cell cycle and PI3K-AKT pathways seem critical in ESCC. These results establish a comprehensive genomic landscape of ESCC and provide potential targets for precision treatment and prevention of the cancer.

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“…Fetal development is one of the key and pivotal factors regulating the differentiation and proliferation of neural progenitor cells. The expression of the RBPJ gene in lung and prostate cancer cells was previously silenced by Lv et al (46) and Xue et al (47), and the results suggested that the downregulation of RBPJ expression leads to a significant decrease in the growth of cancer cells, which suggests that RBPJ serves a downstream role in the Notch signaling pathway and appears to be essential for the functional activation of Notch signaling.…”

Section: Discussionmentioning

confidence: 93%

Abnormal expression and mutation of the RBPJ gene may be involved in CD59‑ clonal proliferation in paroxysmal nocturnal hemoglobinuria

Liu

Wang

et al. 2019

Exp Ther Med

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Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal proliferative disease of hematopoietic stem cells. Various gene mutations, including the phosphatidylinositol glycan anchor biosynthesis class A (PIG-A) gene, may contribute to the proliferation of PNH clones. In order to explore the mechanism of PNH clone proliferation, a study was performed on 13 patients with PNH who underwent whole exome sequencing. The frequency of mutations in these patients was explored, and an additional 30 patients with PNH were selected for analysis of cluster of differentiation 59-negative (CD59 − ) cells. The mRNA expression of 13 genes, which were selected based on their high frequency in patients with PNH and the fact that they met four screening conditions, was determined in these CD59 − cells. Cell proliferation, apoptosis and cell cycle were evaluated upon knocking down the recombinant signal binding protein of immunoglobulin κJ region (RBPJ) gene in 5 patients in vitro . The detection rate of PIG-A gene mutation was 61.54% (8/13), and additional mutations in somatic genes were detected, including RBPJ, zinc finger protein 717, polycomb repressive complex 2 subunit and tet methylcytosine dioxygenase. Upon screening according to the mutation frequency and expression level, the present study focused on the RBPJ gene. The expression level of RBPJ in CD59 − cells was apparently higher than that in CD59 + cells and normal controls which was significantly correlated with clinical data. Furthermore, the expression of RBPJ in PNH primary cells could be effectively inhibited by small interfering RNA-RBPJ. Once the expression of RBPJ decreased remarkably, the apoptotic rate increased gradually, while cell proliferation activity decreased with transfection time and cells were blocked in G0/G1 phase. In conclusion, mutations and abnormal expression of the RBPJ gene may participate in the abnormal proliferation of PNH clones.

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Inhibition of Recombining Binding Protein Suppressor of Hairless (RBPJ) Impairs the Growth of Prostate Cancer

Cited by 11 publications

References 46 publications

Notch-effector CSL promotes squamous cell carcinoma by repressing histone demethylase KDM6B

Notch-effector CSL promotes squamous cell carcinoma by repressing histone demethylase KDM6B

Genomic analysis of oesophageal squamous-cell carcinoma identifies alcohol drinking-related mutation signature and genomic alterations

Abnormal expression and mutation of the RBPJ gene may be involved in CD59‑ clonal proliferation in paroxysmal nocturnal hemoglobinuria

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