The proto-oncogene Bcl3 induces immune checkpoint PD-L1 expression, mediating proliferation of ovarian cancer cells

Zou, Yue; Uddin, Mohammad M.; Padmanabhan, Sveta; Zhu, Yan; Bu, Pengli; Vančura, Aleš; Vancurova, Ivana

doi:10.1074/jbc.ra118.004084

Cited by 48 publications

(57 citation statements)

References 66 publications

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“…However, future researches are required regarding the regulatory possibility of the NF‐κB signalling pathway in ovarian cancer. Critically, the proto‐oncogene BCL3 has been detected to express highly in human ovarian cancer tissues where ovarian cancer cell survival, proliferation and migration are promoted, supporting our results with regard to the rescue properties of silencing BCL3.…”

Section: Discussionsupporting

confidence: 87%

“…CP can function as a tumour progression marker of epithelial ovarian cancer due to its significantly higher expression in the ascitic fluids of patients with intrinsic chemoresistance . BCL3 has been acknowledged as another important proto‐oncogene in context of ovarian cancer that a high BCL3 expression has been evident in human ovarian cancer tissue where ovarian cancer cell survival, proliferation and migration are promoted, respectively . BCL3 involves in key oncogenic pathways in association with cell death and apoptosis in solid tumours and can inhibit ovarian cancer proliferation through interplay with microRNA‐125b (miR‐125b) .…”

Section: Introductionmentioning

confidence: 99%

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Knockdown of long non‐coding RNA LINC00176 suppresses ovarian cancer progression by BCL3‐mediated down‐regulation of ceruloplasmin

Dai

Niu

Feng

2019

J Cellular Molecular Medi

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Ovarian cancer is a common malignancy among women with some clinically approved diagnostic coding gene biomarkers. However, long non‐coding RNAs (lncRNAs) have been indicated to play an important role in controlling tumorigenesis of ovarian cancer. Hereby, the aim of the study was to uncover the function of lncRNA LINC00176 in the development and progression of ovarian cancer by regulating ceruloplasmin (CP). Bioinformatics prediction in combination with RT‐qPCR analysis for the expression pattern of LINC00176 revealed that LINC00176 was highly expressed in ovarian cancer tissues as well as in ovarian cancer cell lines, respectively. LINC00176 was predominantly localized in the nucleus. Delivery of si‐LINC00176, oe‐LINC00176, si‐BCL3 and si‐CP plasmids was conducted to explore the effects of LINC00176 on ovarian cancer. Promoted proliferation, migration and invasion along with reduced apoptosis were observed in cells treated with oe‐LINC00176, while si‐BCL3 and si‐CP were able to block the promoting effects. Investigations with regard to the correlation between LINC00176 and promoter region of CP turned out to be positive via B‐cell CLL/lymphoma 3 (BCL3) by means of dual‐luciferase reporter gene assay, ChIP and RIP assays. Furthermore, oncogenic properties of the LINC00176/BCL3/CP axis were also demonstrated by tumour formation in vivo generated upon injecting cells in nude mice. Our results demonstrate that restored LINC00176 initiates tumorigenesis in ovarian cancer by increasing CP expression via recruiting BCL3, the mechanism of which represented a potential and promising therapeutic target for the disease.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Knockdown of long non‐coding RNA LINC00176 suppresses ovarian cancer progression by BCL3‐mediated down‐regulation of ceruloplasmin

Dai

Niu

Feng

2019

J Cellular Molecular Medi

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“…EP300 has been shown to affect tumor-propagating physical properties [35], in concordance with the observed difference in 2D adherent culture and 3D suspension culture in the current study. Differences we observed in tumorsphere formation capacity after EP300 KD between different TNBC cell lines could be due to technical differences in gene knock down (stable vs. transient) or have distinct biological reasons such as the claudin-low versus basal-like subtypes [36].…”

Section: Discussionmentioning

confidence: 87%

EP300 Knockdown Reduces Cancer Stem Cell Phenotype, Tumor Growth and Metastasis in Triple Negative Breast Cancer

Ring¹,

Kaur

Lang

2020

Preprint

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Background: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype with basal features, lacking the expression of receptors targeted successfully in other breast cancer subtypes. Treatment response to adjuvant and neoadjuvant chemotherapy is often short-lived and metastatic spread occurs at higher rates than other subtypes within the first five years after diagnosis. TNBCs exhibit stem cell features and are enriched for cancer stem cell (CSC) populations. E1A Binding Protein P300 (EP300) is a large protein with multiple cellular functions, including as an effector in stem cell biology.Methods: We used a genetic knockdown (KD) model of EP300 in TNBC cell lines to investigate the effect on CSC phenotype, tumor growth and metastasis. Side population assay and tumorsphere suspension culture were used in vitro. Xenograft mouse models were used for in vivo studies. We performed in silico analysis of publicly available gene expression data sets to investigate CSC gene expression and molecular pathways as well as survival outcomes associated with EP300 expression in patients with TNBC and basal-like BC.Results: EP300 KD abolished the CSC phenotype by reducing ABCG2 expression, side population cells and tumorsphere formation capacity in vitro as well as tumor formation in a xenograft mouse model in vivo. Metastatic capacity was markedly reduced in EP300 KD cells in vivo, with no detection of circulating tumor cells. TCGA data analysis demonstrated that genes positively correlated with EP300 expression in TNBC and basal-like BC were associated with CSC biology. Survival analysis demonstrated that EP300 expression predicts poor recurrence free survival in TNBC and basal BC. Conclusion: We report a novel oncogenic role for EP300 in driving CSC phenotype representing a potential target to address tumor initiation and metastatic spread in TNBC and basal-like BC. EP300 might serve as a prognostic marker and potential therapeutic target in TNBC.

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“…It plays a decisive role in promoting cell migration [44]. Bcl3 is abnormally expressed in several types of solid tumors, such as breast [45], endometrial [46], colorectal [47], nasal atrial [48], cervical [49] and ovarian cancer [50]. Bcl-3 nuclear expression is negatively correlated with the survival of CRC patients [47].…”

Section: Discussionmentioning

confidence: 99%

Identification of prognostic-associated genes in colorectal cancer based on genome-wide expression profiles

Hou¹,

Zhang²,

Chen³

et al. 2020

Preprint

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Background: Colorectal cancer (CRC), a severe disease in the world. The dysregulation of genes plays a significant role in cancer. Method: In the present study, we first identified differentially expressed genes (DEGs) of CRC in the GSE71187 data set from the Gene Expression Omnibus (GEO) database. And through GO terminology and Gene and Genome (KEGG) pathway, the up-regulated DEG and down-regulated genes were enriched. Then, we selected hub genes and studied their related prognostic value through protein-protein interaction (PPI) network and integrated bioinformatics analysis. Finally, 7 genes with prognostic value were obtained by survival analysis and multivariate Cox proportional hazards regression models, as well as verified in the Oncomine and UALCAN database.Result: A total of 3,588 DEGs were identified with 1,474 upregulated and 3,114 downregulated. Then, GO terms and Genes and Genomes (KEGG) pathway analysis revealed that upregulated DEGs and down-regulated genes were mainly involved in important GO terms and KEGG pathway, for example, defense response to other organism, leukocyte differentiation and epidermis developmen. In the PP network analysis, 6 hub modules and 86 module genes were identified. In the end, 7 genes with prognostic value were obtained through survival and multi-factor analysis. They have significant differences in varying degrees at the level of DNA, mRNA and protein.Conclusion: The results of the study may provide novel insight into the genes and associated pathways involved in CRC, and aid the identifcation of novel therapeutic targets and prognostic marker of CRC.

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The proto-oncogene Bcl3 induces immune checkpoint PD-L1 expression, mediating proliferation of ovarian cancer cells

Cited by 48 publications

References 66 publications

Knockdown of long non‐coding RNA LINC00176 suppresses ovarian cancer progression by BCL3‐mediated down‐regulation of ceruloplasmin

Knockdown of long non‐coding RNA LINC00176 suppresses ovarian cancer progression by BCL3‐mediated down‐regulation of ceruloplasmin

EP300 Knockdown Reduces Cancer Stem Cell Phenotype, Tumor Growth and Metastasis in Triple Negative Breast Cancer

Identification of prognostic-associated genes in colorectal cancer based on genome-wide expression profiles

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