E2F1 transcriptionally regulates CCNA2 expression to promote triple negative breast cancer tumorigenicity

Lu, Yongbin; Su, Fei; Yang, Hui; Xiao, Yi; Zhang, Xiaobin; Su, Hongxin; Zhang, Tao; Bai, Yana; Ling, Xiaoling

doi:10.3233/cbm-210149

Cited by 19 publications

(15 citation statements)

References 26 publications

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“…In addition, E2F1 regulates the expression of various cytokines and growth factor receptors to establish a feedback mechanism ( Ertosun et al, 2016 ). A recent research from Lu et al revealed that E2F1 transcriptionally regulated cell cycle regulator cyclin A2 (CCNA2) expression to promote tumorigenicity of TNBC ( Lu et al, 2021 ). Here, further study based on a dual-luciferase assay and a ChIP-qPCR assay revealed that RFWD3 could facilitate the binding of E2F1 to the BIRC5 promoter and transcriptionally activate BIRC5 by interacting with E2F1 in HCT-116 cells.…”

Section: Discussionmentioning

confidence: 99%

RFWD3 Participates in the Occurrence and Development of Colorectal Cancer via E2F1 Transcriptional Regulation of BIRC5

Xiao

Fan

et al. 2021

Front. Cell Dev. Biol.

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Objectives: Colorectal cancer (CRC) is one of the most common human malignancies. It was reported that the alterations in the DNA damage response (DDR) pathways are emerging as novel targets for treatment across different cancer types including CRC. RFWD3 plays a critical role in replication protein A (RPA)-mediated DNA damage in cancer cells. More importantly, RFWD3 can response to DNA damage by positively regulating p53 stability when the G1 cell cycle checkpoint is activated. However, the functional significance of RFWD3 in CRC has not been reported in the existing documents.Materials and Methods: Here, we revealed high expression of RFWD3 in CRC tissues by IHC analysis and The Cancer Genome Atlas (TCGA) database. Besides, overexpression of RFWD3 in CRC cell lines was also confirmed by qRT-PCR and western blot assay. The Celigo cell counting method and wound-healing/transwell migration assay were applied to evaluate CRC cell proliferation and migration. The tumor growth indicators were quantified in nude mice xenografted with shRFWD3 and shCtrl RKO cells.Results: The results indicated that RFWD3 knockdown restricted CRC development in vitro and in vivo. In exploring the downstream mechanism of RFWD3’s action, we found that RFWD3 could transcriptionally activate BIRC5 by interacting with E2F transcription factor 1 (E2F1). Accordingly, we identified BIRC5 as a downstream gene of RFWD3 regulating CRC. Subsequent loss- and gain- of function experiments demonstrated that upon overexpressing BIRC5 in RKO cells with down-regulated RFWD3, the inhibitory effects of cell proliferation, migration and colony formation could be reversed, while the capacity of cell apoptosis was ameliorated, suggesting that the effects of RFWD3 depletion was mainly due to BIRC5 suppression.Conclusion: Taken together, this study revealed that RFWD3 participates in the occurrence and development of colorectal cancer via E2F1 transcriptional regulation of BIRC5.

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Section: Discussionmentioning

confidence: 99%

RFWD3 Participates in the Occurrence and Development of Colorectal Cancer via E2F1 Transcriptional Regulation of BIRC5

Xiao

Fan

et al. 2021

Front. Cell Dev. Biol.

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“…Cyclin A2 dominates the longest period of time in the late G1 phase and could bind to CDK2. Previous study has demonstrated that overexpression of cyclin A2 promotes TNBC proliferation, invasion, and migration while inhibiting apoptosis [44]. Cyclin D1 has been proven as an oncogenic factor since upregulation of cyclin D1 was related to poor cancer prognosis [45].…”

Section: Discussionmentioning

confidence: 99%

Tanshinone IIA Inhibits Triple-Negative Breast Cancer Cells MDA-MB-231 via G Protein-Coupled Estrogen Receptor- (GPER-) Dependent Signaling Pathway

Liu

et al. 2023

Disease Markers

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Due to the lack of classic estrogen receptors, there has been a shortage of targeted therapy for triple-negative breast cancer (TNBC), resulting in a poor prognosis. However, the newly discovered G protein-coupled estrogen receptor (GPER) has been found to be expressed in TNBC cells. Salvia miltiorrhiza (Danshen) is an essential Chinese medicine for gynecological disorders, and its component tanshinone IIA (Tan IIA) exerts an anticancer effect. Therefore, this study attempted to investigate whether GPER is involved in the inhibitory effect of Tan IIA on TNBC. We applied various databases and GO pathway analysis to predict the possible mechanism of Tan IIA. We identified 39 overlapping targets, including c-Jun, c-Fos, and caspase-3, and enriched cell cycle-related pathways. Next, we demonstrated the strong binding ability of Tan IIA to GPER by molecular docking assay. In the subsequent validation tests, Cell Counting Kit-8 (CCK8) assay showed that Tan IIA inhibited proliferation of MDA-MB-231 cells time and dose dependently without affecting normal cells. Using Transwell plate, flow cytometry, and Western blot assays, we showed that Tan IIA inhibited migration and induced apoptosis of MDA-MB-231 dose dependently. Importantly, protein expressions of GPER, epidermal growth factor receptor (EGFR), extracellular regulated protein kinases (ERK), c-Fos, and c-Jun were all decreased by Tan IIA dose dependently. Administration of GPER inhibitor partly abolished these effects. Furthermore, nuclear translocation of c-Fos and c-Jun as well as cell cycle-related proteins was downregulated by Tan IIA dose dependently. In summary, Tan IIA could inhibit the proliferation and migration of MDA-MB-231 cells and induce apoptosis, and the possible mechanism may be the regulation of GPER-mediated pathways, suggesting that GPER could be a therapeutic target for TNBC.

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“…Hub proteins could be used for the development of therapeutic intervention. Cyclin A2 (CCNA2) regulates the cell cycle and contributes to tumor growth ( 47 ). Cyclin B1 (CCNB1) is a crucial mitosis initiator and controller ( 48 ).…”

Section: Discussionmentioning

confidence: 99%

Blood transcriptome analysis revealed the crosstalk between COVID-19 and HIV

2022

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BackgroundThe severe coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has resulted in the most devastating pandemic in modern history. Human immunodeficiency virus (HIV) destroys immune system cells and weakens the body’s ability to resist daily infections and diseases. Furthermore, HIV-infected individuals had double COVID-19 mortality risk and experienced worse COVID-related outcomes. However, the existing research still lacks the understanding of the molecular mechanism underlying crosstalk between COVID-19 and HIV. The aim of our work was to illustrate blood transcriptome crosstalk between COVID-19 and HIV and to provide potential drugs that might be useful for the treatment of HIV-infected COVID-19 patients.MethodsCOVID-19 datasets (GSE171110 and GSE152418) were downloaded from Gene Expression Omnibus (GEO) database, including 54 whole-blood samples and 33 peripheral blood mononuclear cells samples, respectively. HIV dataset (GSE37250) was also obtained from GEO database, containing 537 whole-blood samples. Next, the “Deseq2” package was used to identify differentially expressed genes (DEGs) between COVID-19 datasets (GSE171110 and GSE152418) and the “limma” package was utilized to identify DEGs between HIV dataset (GSE37250). By intersecting these two DEG sets, we generated common DEGs for further analysis, containing Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) functional enrichment analysis, protein-protein interaction (PPI) analysis, transcription factor (TF) candidate identification, microRNAs (miRNAs) candidate identification and drug candidate identification.ResultsIn this study, a total of 3213 DEGs were identified from the merged COVID-19 dataset (GSE171110 and GSE152418), and 1718 DEGs were obtained from GSE37250 dataset. Then, we identified 394 common DEGs from the intersection of the DEGs in COVID-19 and HIV datasets. GO and KEGG enrichment analysis indicated that common DEGs were mainly gathered in chromosome-related and cell cycle-related signal pathways. Top ten hub genes (CCNA2, CCNB1, CDC20, TOP2A, AURKB, PLK1, BUB1B, KIF11, DLGAP5, RRM2) were ranked according to their scores, which were screened out using degree algorithm on the basis of common DEGs. Moreover, top ten drug candidates (LUCANTHONE, Dasatinib, etoposide, Enterolactone, troglitazone, testosterone, estradiol, calcitriol, resveratrol, tetradioxin) ranked by their P values were screened out, which maybe be beneficial for the treatment of HIV-infected COVID-19 patients.ConclusionIn this study, we provide potential molecular targets, signaling pathways, small molecular compounds, and promising biomarkers that contribute to worse COVID-19 prognosis in patients with HIV, which might contribute to precise diagnosis and treatment for HIV-infected COVID-19 patients.

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E2F1 transcriptionally regulates CCNA2 expression to promote triple negative breast cancer tumorigenicity

Cited by 19 publications

References 26 publications

RFWD3 Participates in the Occurrence and Development of Colorectal Cancer via E2F1 Transcriptional Regulation of BIRC5

RFWD3 Participates in the Occurrence and Development of Colorectal Cancer via E2F1 Transcriptional Regulation of BIRC5

Tanshinone IIA Inhibits Triple-Negative Breast Cancer Cells MDA-MB-231 via G Protein-Coupled Estrogen Receptor- (GPER-) Dependent Signaling Pathway

Blood transcriptome analysis revealed the crosstalk between COVID-19 and HIV

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