RETRACTED ARTICLE: p300 promotes proliferation, migration, and invasion via inducing epithelial-mesenchymal transition in non-small cell lung cancer cells

Hou, Xue; Gong, Run; Zhan, Jie; Zhou, Ting; Ma, Yuxiang; Zhao, Yuanyuan; Zhang, Yaxiong; Chen, Gang; Zhang, Zhonghan; Ma, Shijing; Chen, Xi; Gao, Fangfang; Hong, Shaodong; Luo, Fan; Fang, Wenfeng; Yang, Yunpeng; Huang, Yan; Chen, Likun; Yang, Hao‐Xian; Zhang, Li

doi:10.1186/s12885-018-4559-3

Cited by 35 publications

(35 citation statements)

References 23 publications

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“…In agreement with ndings that EP300 increases migratory potential and invasiveness of cancer cells [39], [40], we demonstrated reduced lung colonization and distant metastasis as well as circulating tumor cells via EP300 KD in TNBC cells.…”

Section: Discussionsupporting

confidence: 92%

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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Section: Discussionsupporting

confidence: 92%

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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“…[ 27 ] EP300 has been proved to be upregulated in several malignancies, such as non-small cell lung cancer, colorectal carcinomas, hepatocellular carcinoma. [ 28 – 30 ] A recent study demonstrated that mutation of EP300 is correlated with higher tumor mutation burden (TMB) and promotes antitumor immunity in bladder cancer patients. [ 31 ] Dou et al [ 32 ] showed that phosphorylation of EP300 associated with liver metastasis.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel biomarkers and small-molecule compounds for nasopharyngeal carcinoma with metastasis

Liu

et al. 2020

Medicine

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The purpose of this study was to investigate novel biomarkers and potential mechanisms in nasopharyngeal carcinoma (NPC) patients with metastasis. Two microarray datasets (GSE103611 and GSE36682) were obtained from GEO database, differentially expressed genes (DEGs) and differentially expressed miRNA (DEMs) were identified, Gene ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted with DEGs and DEMs targeted genes. Protein–protein interactions (PPI) network of the DEGs and DEMs targeted genes were constructed, furthermore, Connectivity Map (CMap) database was applied to select the potential drugs with therapeutic effects. Overall, we identified 396 upregulated and 19 downregulated DEGs. Additionally, we identified 1 upregulated DEM, miR-135b, and a downregulated DEM, miR-574-5p. Functional enrichment analysis indicated that both DEGs and DEMs targeted genes participated in biological process (BP) of regulation of transcription from RNA polymerase II promoter, DNA-templated positive regulation of transcription, and Epstein-Barr virus infection signaling pathway. Besides, upregulated EP300 gene was a hub node both in DEGs and DEMs target genes. CMap database analysis indicated that sanguinarine, verteporfin, and chrysin are potential drugs for prevention and treatment of NPC metastasis. In summary, the common hub gene, biological process and pathway identified in the study provided a novel insight into the potential mechanism of NPC metastasis. Furthermore, we identified several possible small molecule compounds for treatment of NPC metastasis.

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“…Numerous studies have demonstrated p300 was associated with enhanced EMT and correlates with poor prognosis in these cancers [41,43]. Overexpression of p300 promotes cell proliferation, migration, and invasion in NSCLC cells [42]; knockdown of p300 inhibited EMT, invasion and other malignant events of HCC cells [43]. However, we must note that p300 may act as a suppressor of tumor metastasis in some cancers.…”

Section: Discussionmentioning

confidence: 89%

“…Abnormal expression of p300 has been identi ed in esophageal squamous carcinoma, NSCLC cells and hepatocellular carcinoma [41][42][43]. Numerous studies have demonstrated p300 was associated with enhanced EMT and correlates with poor prognosis in these cancers [41,43].…”

Section: Discussionmentioning

confidence: 99%

P300-dependent acetylation of histone H3 is required for EGFR-mediated HMGA2 transcription in hepatocellular carcinoma

Liang

Niu

Wang

et al. 2020

Preprint

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Abstract Background High-mobility group protein A2 (HMGA2) is highly expressed in hepatocellular carcinoma cells and contributes to tumor metastasis and poor patient survival. However, the molecular mechanism of HMGA2 transcriptional regulation in hepatocellular carcinoma cells remains largely unclear. Methods Mouse model of lung metastasis was used to evaluate the effects of HMGA2 on hepatocellular carcinoma. DEN-induced rat model of hepatocellular carcinoma was used to measure the expression of HMGA2 and histone H3 acetylation. Immunohistochemistry was used to analyze the expression levels of HMGA2 in 39 matched HCC tissues and adjacent non-tumor tissues. Real-time PCR, Western blotting and Chromatin Immunoprecipitation assay were used to investigate the underlying mechanisms by which HMGA2 overexpression in hepatocellular carcinoma cells. Result Compared with adjacent non-tumour tissues, the expression of HMGA2 was significantly upregulated in human HCC tumor tissues. Moreover, We demonstrated that the expression HMGA2 was upregulated in HCC, and the elevated HMGA2 could promote tumor metastasis. Incubation HCC cells with Epidermal growth factor (EGF) could promote the expression of HMGA2 mRNA and protein. Knockdown of p300 can reverse EGF-induced HMGA2 expression and histone H3-K9 acetylation, while a phosphorylation-mimic p300 S1834D mutant can stimulate HMGA2 expression as well as H3-K9 acetylation in HCC cells. Furthermore, we identified p300-mediated H3-K9 acetylation participates in EGF-induced HMGA2 expression in HCC. In addition, the levels of H3-K9 acetylation positively correlated with the expression levels of HMGA2 in human HCC specimens. Conclusion p300-dependent acetylation of histone H3 is required for EGFR-mediated HMGA2 transcription in hepatocellular carcinoma.

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RETRACTED ARTICLE: p300 promotes proliferation, migration, and invasion via inducing epithelial-mesenchymal transition in non-small cell lung cancer cells

Cited by 35 publications

References 23 publications

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

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

Identification of novel biomarkers and small-molecule compounds for nasopharyngeal carcinoma with metastasis

P300-dependent acetylation of histone H3 is required for EGFR-mediated HMGA2 transcription in hepatocellular carcinoma

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