Ki-67 promotes carcinogenesis by enabling global transcriptional programmes
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ABSTRACT:
PROVIDER: PRJNA684921 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13168827.fastq.gz | Fastqsanger.gz | |||
| SRR13168828.fastq.gz | Fastqsanger.gz | |||
| SRR13168829.fastq.gz | Fastqsanger.gz | |||
| SRR13168830.fastq.gz | Fastqsanger.gz | |||
| SRR13168831.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-02-18 | GSE163114 | GEO
Project description:Antigen Ki-67 is a nuclear protein expressed in proliferating mammalian cells. It is widely used in cancer histopathology but its functions remain unclear. Here, we show that Ki-67 controls heterochromatin organisation. Altering Ki-67 expression levels did not significantly affect cell proliferation in vivo. Ki-67 mutant mice developed normally and cells lacking Ki-67 proliferated efficiently. Conversely, upregulation of Ki-67 expression in differentiated tissues did not inhibit cell cycle arrest. Ki-67 interactors included proteins involved in nucleolar processes and chromatin regulators. Ki-67 depletion disrupted nucleologenesis but did not inhibit pre-rRNA processing. In contrast, it altered gene expression. Ki-67 silencing also had wide-ranging effects on chromatin organisation, disrupting heterochromatin compaction and long-range genomic interactions. Trimethylation of histone H3K9 and H4K20 at heterochromatin was strongly reduced. Overexpression of human or Xenopus Ki-67 induced ectopic heterochromatin formation. Altogether, our results suggest that Ki-67 expression in proliferating cells spatially organises heterochromatin, thereby controlling gene expression.
2018-10-26 | PXD003551 | Pride
Project description:Ki-67 molecular functions and properties have remained quite obscure for a long time, despite its importance as a major proliferation marker in clinic. Only recently it has been shown that Ki-67 has a major role in the formation of the mitotic chromosome periphery compartment, and it is a protein phosphatase 1 (PP1) binding protein. Understanding Ki-67 functions at different stages of the cell cycle has been so far hindered by the fact that the different phenotypes observed in cells upon Ki-67 depletion could be the outcome of secondary effects. Here, by using Auxin-inducible-degron (AID) system, we show that Ki-67 degradation at the G1/S boundary causes the disassembly of the replication machinery and leads to DNA damage. This triggers the interferon response and causes replication delay. Our results support the model whereby Ki-67 contributes to replication forks protection, and it is important for timely DNA replication and genome maintenance.
2024-04-13 | PXD037513 | Pride
Project description:Transcriptional profiling of isogenic human cervical cancer cell line HCT-116, comparing cells treated with control shRNA or with Ki-67 shRNA, grown either in vitro or as tumours in nude mice. The aim was to assess effects of loss of Ki-67 on gene expression during exponential cell growth and in tumours
2021-02-18 | GSE162365 | GEO
Project description:Raw RNA-seq data from control and Ki-67-depleted HCT116 human colon cancer cells
2021-07-23 | GSE159160 | GEO
Project description:Ki-67 is highly expressed in proliferating cells, characteristic that made the protein a very important marker widely used in the clinic. However, its molecular functions and properties have remained quite obscure for a long time. Only recently important discoveries have shed some light on Ki-67 function and shown that Ki-67 has a major role in the formation of mitotic chromosome periphery compartment, it is associated with protein phosphatase one (PP1) and regulates chromatin structure in both interphase and mitosis. However, it is still difficult to understand the specific molecular function of this protein since the different phenotypes could be the outcome of secondary effects. In fact, the studies so far conducted have used either RNAi or knock-out cells: the former could lead to phenotypes which are the sum of a cascade of complex events while the latter could be the outcome of compensatory mechanisms taking place. To address these problems, we have generated a cell line system for the rapid manipulation of Ki-67 by introducing an Auxin-inducible-degron (AID) tag in both alleles of the endogenous Ki-67 gene in HCT116 cells. This AID system allows rapid protein depletion by the addition of Auxin.
2024-04-07 | E-MTAB-12279 | biostudies-arrayexpress
Project description:Purpose: The management of adrenocortical tumors (ACTs) is complex, compounded by the difficulty in discriminating benign from malignant tumors using conventional histology. The Weiss score is the current most widely used system for ACT diagnosis but it has limitations, particularly with ACTs with a score of 3. The am of this study was to identify molecular markers whose expression can discriminate adrenocortical carcinomas (ACCs) from adrenocortical adenomas (ACAs) by microarray gene expression profiling and to determine their clinical applicability by using immunohistochemistry (IHC). Experimental design: Microarray gene expression profiling was used to identify 7 molecular markers which were significantly differentially expressed between ACCs and ACAs. These results were confirmed with quantitative PCR for all 7 genes and IHC for 3 protein. Results: Microarray gene expression profiling was able to accurately categorize ACTs into ACCs and ACAs. All 7 genes were strong discriminators of ACCs from ACAs on qPCR. IHC with IGF2, MAD2L1, CCNB1 and Ki-67, but not ACADVL or ALOX15B, had high diagnostic accuracy in differentiating ACCs from ACAs. The best results however were obtained with a combination of IGF2 and Ki-67 with 96% sensitivity and 100% specificity in diagnosing ACCs. Conclusion: Microarray gene expression profiling accurately differentiates ACCs from ACAs. The combination of IGF2 and Ki-67 IHC is also highly accurate in distinguishing between the 2 groups and is particularly helpful in ACTs with Weiss score of 3. Keywords: Adrenocortical carcinoma, adrenocortical adenoma, differential gene expression, immunohistochemistry, qPCR
2009-07-29 | GSE12368 | GEO
Project description:Ki-ras gene mutations are involved in the carcinogenesis of acute myeloid leukemia, melanoma and different carcinomas. In order to define potential mutation-specific therapeutic targets, expression profiling analyses were performed using stable transfected NIH3T3 cells carrying different ki-ras gene mutations. Maybe, this analysis allows the discorvery of ras-associated cellular mechanisms, which might lead to the identification of physiological targets for pharmacological interventions of the treatment of Ki-ras-associated human tumors. Keywords: cDNA microarray, murine fibroblast, ki-ras mutations, carcinogenesis
2008-08-01 | GSE8372 | GEO
Project description:Ki-ras gene mutations are involved in the carcinogenesis of acute myeloid leukemia, melanoma and different carcinomas. In order to define potential mutation-specific therapeutic targets, expression profiling analyses were performed using stable transfected NIH3T3 cells carrying different ki-ras gene mutations. Maybe, this analysis allows the discorvery of ras-associated cellular mechanisms, which might lead to the identification of physiological targets for pharmacological interventions of the treatment of Ki-ras-associated human tumors. Keywords: cDNA microarray, murine fibroblast, ki-ras mutations, carcinogenesis 4 transfected murine fibroblast cell lines (mock, wt-kras, Asp, Val) were compared to non-transfected cell line. For each of the four comparison 4 chip experiments were performed including 2 dye swaps.
2010-05-25 | E-GEOD-8372 | biostudies-arrayexpress
Project description:Ki-67 is a nuclear protein that is expressed in all proliferating vertebrate cells. Here, we demonstrate that, although Ki-67 is not required for cell proliferation, its genetic ablation inhibits each step of tumor initiation, growth, and metastasis. Mice lacking Ki-67 are resistant to chemical or genetic induction of intestinal tumorigenesis. In established cancer cells, Ki-67 knockout causes global transcriptome remodeling that alters the epithelial-mesenchymal balance and suppresses stem cell characteristics. When grafted into mice, tumor growth is slowed, and metastasis is abrogated, despite normal cell proliferation rates. Yet, Ki-67 loss also down-regulates major histocompatibility complex class I antigen presentation and, in the 4T1 syngeneic model of mammary carcinoma, leads to an immune-suppressive environment that prevents the early phase of tumor regression. Finally, genes involved in xenobiotic metabolism are down-regulated, and cells are sensitized to various drug classes. Our results suggest that Ki-67 enables transcriptional programs required for cellular adaptation to the environment. This facilitates multiple steps of carcinogenesis and drug resistance, yet may render cancer cells more susceptible to antitumor immune responses.
| S-EPMC7958263 | biostudies-literature