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Down-regulation of Polo-like kinase 4 (PLK4) induces G1 arrest via activation of the p38/p53/p21 signalling pathway in bladder

ABSTRACT: Down-regulation of Polo-like kinase 4 (PLK4) induces G1 arrest via activation of the p38/p53/p21 signalling pathway in bladder

PROVIDER: PRJNA750144 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15265924.fastq.gz	Fastqsanger.gz
	SRR15265925.fastq.gz	Fastqsanger.gz
	SRR15265926.fastq.gz	Fastqsanger.gz
	SRR15265927.fastq.gz	Fastqsanger.gz

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Similar Datasets

Down-regulation of Polo-like kinase 4 (PLK4) induces G1 arrest via activation of the p38/p53/p21 signalling pathway in bladder

Project description:We demonstrate that Polo-like kinase 4(PLK4) is overexpressed in human bladder cancer (BC) cell lines and tissues, and its overexpression correlates with poor prognosis. PLK4 inhibition suppresses BC cell growth and induces G1 phase arrest via activating p38/p53/p21 pathway in vitro and in vivo. The data suggest that PLK4 might serve as a novel molecular target for BC treatment.

2021-07-29 | GSE180958 | GEO

Down-regulation of Polo-like kinase 4 (PLK4) induces G1 arrest via activation of the p38/p53/p21 signaling pathway in bladder cancer.

Project description:Polo-like kinase 4 (PLK4) has been reported to contribute to tumor growth, invasion, and metastasis. However, the role of PLK4 in human bladder cancer (BC) remains unclear. Here, we demonstrate the regulatory function of PLK4 in human BC progression. PLK4 is overexpressed in BC cell lines and tissues, and its overexpression correlated with poor prognosis. Our transcriptome analysis combined with subsequent functional assays indicated that PLK4 inhibition can suppress BC cell growth and induce cell cycle arrest at G1 phase via activation of the p38/p53/p21 pathway in vitro and in vivo. Overall, our data suggest that PLK4 is a critical regulator of BC cell proliferation, and thus, it may have potential as a novel molecular target for BC treatment.

| S-EPMC8409300 | biostudies-literature

Imperatorin induces autophagy and G0/G1 phase arrest via PTEN-PI3K-AKT-mTOR/p21 signaling pathway in human osteosarcoma cells in vitro and in vivo

Project description:Osteosarcoma is the third most common cancer in adolescence and the first common primary malignant tumor of bone. The long-term prognosis of osteosarcoma, especially for unresectable and metastatic tumors, still remains unsatisfactory in the past decades. In this study, we systematically investigated the antitumor effect of imperatorin (IMP), a small molecule extracted from Angelica dahurica, in human osteosarcoma cells. The results showed that IMP triggered time-dependent and dose-dependent inhibition of tumor growth mainly by inducing autophagy promotion and G0/G1 phase arrest in vitro and in vivo. Besides, IMP treatment elevated the expression level of PTEN and p21, down-regulated the phosphorylation of AKT and mTOR. In contrast, the inhibition of PTEN using Bpv (HOpic), a potential and selective inhibitor of PTEN, concurrently rescued IMP-induced autophagy promotion, cell cycle arrest and inactivation of PTEN-PI3K-AKT-mTOR/p21 pathway. Taken together, our data revealed that imperatorin induced autophagy and cell cycle arrest through PTEN-PI3K-AKT-mTOR/p21 signaling pathway by targeting and up-regulating PTEN in human osteosarcoma cells. Hence, imperatorin is a desirable candidate for clinical treatments of osteosarcoma.

2021-12-23 | GSE180321 | GEO

Use of the Polo-like kinase 4 (PLK4) inhibitor centrinone to investigate intracellular signaling networks using SILAC-based phosphoproteomics_C4PR

Project description:Polo-like kinase 4 (PLK4) is the master regulator of centriole duplication in metazoan organisms. Catalytic activity and protein turnover of PLK4 are tightly coupled in human cells, since changes in PLK4 concentration and catalysis have profound effects on centriole duplication and supernumerary centrosomes, which are associated with aneuploidy and cancer. Recently, PLK4 has been targeted with a variety of small molecule kinase inhibitors exemplified by centrinone, which induces inhibitory effects on PLK4 and can lead to on-target centrosome depletion. Despite this, relatively few PLK4 substrates have been identified unequivocally in human cells, and the extent of PLK4 signalling remains poorly characterised. We report an unbiased mass spectrometry-based quantitative analysis of cellular protein phosphorylation in stable PLK4-expressing human cells exposed to the small molecule inhibitor centrinone. PLK4 phosphorylation was itself sensitive to brief exposure to centrinone, resulting in PLK4 stabilization. A drug-resistant PLK4 mutant (G95R) confirmed several on-target effects of the compound towards PLK4. Using this experimental system, we report hundreds of centrinone-regulated phosphoproteins in U2OS cells, including centrosomal and cell cycle proteins and a variety of likely non cell-cycle substrates. Surprisingly, sequence interrogation of ~300 significantly downregulated phosphoproteins reveals an extensive network of centrinone-sensitive [Ser/Thr]Pro phosphorylation target sequence motifs, which based on our analysis might be either direct or indirect targets of PLK4. In addition, we confirm NMYC and PTPN12 as new PLK4 substrates, both in vitro and in human cells. Our findings suggest that PLK4 catalytic output directly controls the phosphorylation of a diverse set of cellular proteins, including Pro-directed targets that are likely to be important in PLK4-mediated cell signalling.

2021-06-14 | PXD018704 | Pride

MAGT1 is involved in HeLa cell proliferation through regulating p21 expression, S-phase progress and ERK/p38 MAPK MYC axis

Project description:Background: Magnesium transporter subtype 1 (MAGT1) is involved in animal development and cell differentiation. Thus far, researches on MAGT1 are mainly focused on Cardiomyocyte regulation and differentiation, but rare research has been reported on cell proliferation, especially concerning the underlying molecular mechanisms. Methods: HeLa cells were transiently knock down with different SiRNAs and processed for RNA sequencing and bioinformatics analysis, western blot, real-time PCR as well as cell cycle assays. Results: We showed that cell proliferation was significantly restricted with S-phase arrest in MAGT1 knock down cells, which was further confirmed by the up expression of p21, CCNA1 and CCNB1, while down expression of CCND1, CCNE1 and CDK4. Knocking down MAGT1 also resulted in significant transcriptional expression changes of 1599 target genes analyzed by RNA sequencing. The bioinformatics analysis showed that MAGT1 was related to MAPK signaling pathway. Western blot analysis confirmed that the phosphorylation of ERK1/2 and p38 exhibited a remarkable reduction in MAGT1 downregulated group. Conclusion: MAGT1 is critical in HeLa cell proliferation, S-phase progress and ERK/p38 MAPK signaling pathway, indicating that MAGT1 might be a novel target of anticancer research.

2022-02-02 | GSE166084 | GEO

The p53-regulated long noncoding RNA, lincRNA-p21 promotes the expression of Polycomb target genes and enforces the G1/S checkpoint by activating p21 in cis [ChIP-seq]

Project description:The p53-regulated long non-coding RNA, lincRNA-p21, has been proposed to promote apoptosis and to repress in trans the expression of genes in the p53 transcriptional network. Here, we report the generation of a conditional knockout mouse model developed to further examine lincRNA-p21 function. Using this genetic approach, we find that the primary function of lincRNA-p21 is to activate in cis the expression of its neighboring gene, the cyclin-dependent kinase inhibitor p21. Mechanistically, we show that lincRNA-p21 acts in concert with hnRNP-K as a co-activator for p53-dependent transcription of p21. Additional phenotypes of lincRNA-p21 deficiency, including deregulated expression and altered chromatin state of a set of Polycomb target genes, defective G1/S checkpoint, increased proliferation rates, and enhanced reprogramming efficiency could be attributed to diminished p21 levels. This study reveals a novel paradigm, whereby the long non-coding RNA lincRNA-p21 affects global gene expression and influences events in the p53 tumor suppressor pathway by acting in cis as a locus-restricted transcriptional co-activator for p53-mediated expression of p21. Examination of 2 different histone modifications (H3K4me3 and H3K27me3) in 2 cell types (WT and lincRNA-p21 KO) in the presence and absence of Doxorubicin.

2014-05-22 | E-GEOD-52956 | biostudies-arrayexpress

The p53-regulated long noncoding RNA, lincRNA-p21 promotes the expression of Polycomb target genes and enforces the G1/S checkpoint by activating p21 in cis [RNA-seq]

Project description:The p53-regulated long non-coding RNA, lincRNA-p21, has been proposed to promote apoptosis and to repress in trans the expression of genes in the p53 transcriptional network. Here, we report the generation of a conditional knockout mouse model developed to further examine lincRNA-p21 function. Using this genetic approach, we find that the primary function of lincRNA-p21 is to activate in cis the expression of its neighboring gene, the cyclin-dependent kinase inhibitor p21. Mechanistically, we show that lincRNA-p21 acts in concert with hnRNP-K as a co-activator for p53-dependent transcription of p21. Additional phenotypes of lincRNA-p21 deficiency, including deregulated expression and altered chromatin state of a set of Polycomb target genes, defective G1/S checkpoint, increased proliferation rates, and enhanced reprogramming efficiency could be attributed to diminished p21 levels. This study reveals a novel paradigm, whereby the long non-coding RNA lincRNA-p21 affects global gene expression and influences events in the p53 tumor suppressor pathway by acting in cis as a locus-restricted transcriptional co-activator for p53-mediated expression of p21. mRNAseq in 2 cell types (WT and lincRNA-p21 KO) in the presence and absence of Doxorubicin performed in biological triplicate.

2014-05-22 | E-GEOD-52957 | biostudies-arrayexpress

The p53-regulated long noncoding RNA, lincRNA-p21 promotes the expression of Polycomb target genes and enforces the G1/S checkpoint by activating p21 in cis [RNA-seq]

2014-05-22 | GSE52957 | GEO

The p53-regulated long noncoding RNA, lincRNA-p21 promotes the expression of Polycomb target genes and enforces the G1/S checkpoint by activating p21 in cis [ChIP-seq]

2014-05-22 | GSE52956 | GEO

Genes Predictive of G1 arrest in Melanoma Cell Lines

Project description:Transcriptional profiling of human melanoma cell lines to identify a G1 arrest signature Percentage of cells that arrest in G1 after irradiation was used to identify genes predictive of response

2012-08-13 | E-GEOD-40047 | biostudies-arrayexpress

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