Targeting TIP60 inhibits tumorigenesis in non-small cell lung cancer [RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA854150 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19899303.fastq.gz | Fastqsanger.gz | |||
| SRR19899304.fastq.gz | Fastqsanger.gz | |||
| SRR19899305.fastq.gz | Fastqsanger.gz | |||
| SRR19899306.fastq.gz | Fastqsanger.gz | |||
| SRR19899307.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Targeting TIP60 inhibits tumorigenesis in non-small cell lung cancer
| PRJNA854142 | ENA
Project description:Targeting TIP60 inhibits tumorigenesis in non-small cell lung cancer [ChIP-seq]
| PRJNA854151 | ENA
Project description:Histone modifications play crucial roles in transcriptional activation, and aberrant epigenetic changes are associated with oncogenesis. Lysine (K) acetyltransferases 5 (TIP60, also known as KAT5) is reportedly implicated in cancer development, although its function in lung cancer remains unclear. Here we demonstrate that TIP60 knockdown in non-small cell lung cancer cells decreased tumor cell progression. Furthermore, analysis of a mouse lung cancer model with lung-specific conditional Tip60 knockout revealed suppressed tumor formation relative to controls, but no apparent effects on normal lung homeostasis. RNA-seq and ChIP-seq analyses of inducible TIP60 knockdown H1975 cells relative to controls revealed transglutaminase enzyme (TGM5) as downstream of TIP60. In addition, a candidate TIP60 inhibitor suppressed tumor growth in cell culture and in vivo. Taken together, suppression of TIP60 activity shows tumor-specific efficacy against lung cancer, with no overt effect on normal tissues. Our work suggests that targeting TIP60 could be a promising approach in treating lung cancer.
2023-05-08 | GSE207202 | GEO
Project description:Histone modifications play crucial roles in transcriptional activation, and aberrant epigenetic changes are associated with oncogenesis. Lysine (K) acetyltransferases 5 (TIP60, also known as KAT5) is reportedly implicated in cancer development, although its function in lung cancer remains unclear. Here we demonstrate that TIP60 knockdown in non-small cell lung cancer cells decreased tumor cell progression. Furthermore, analysis of a mouse lung cancer model with lung-specific conditional Tip60 knockout revealed suppressed tumor formation relative to controls, but no apparent effects on normal lung homeostasis. RNA-seq and ChIP-seq analyses of inducible TIP60 knockdown H1975 cells relative to controls revealed transglutaminase enzyme (TGM5) as downstream of TIP60. In addition, a candidate TIP60 inhibitor suppressed tumor growth in cell culture and in vivo. Taken together, suppression of TIP60 activity shows tumor-specific efficacy against lung cancer, with no overt effect on normal tissues. Our work suggests that targeting TIP60 could be a promising approach in treating lung cancer.
2023-05-08 | GSE207201 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-05-08 | GSE207203 | GEO
Project description:Genome-wide mapping of TIP60 complex subunits in K562 cells. The objectives of this study are to describe TIP60 genome wide localization, confirm MBTD1 co-localization with already known unique subunits and observe the impact of MBTD1 on TIP60 complex targeting to chromatin. The TIP60 acetyltransferase complex is a key regulator of genome expression and stability. Here, we identified MBTD1 as a new stable subunit of the complex and revealed interesting insights about TIP60 function during the repair of DNA double strand breaks. MBTD1 binds H4K20me1/2, helping TIP60 association to specific promoters but also the DNA repair process by homologous recombination. While pro-end joining factor 53BP1 engages chromatin through simultaneous binding of H4K20me2 and H2AK15ub, TIP60 regulates the resolution of 53BP1 foci after DNA damage through a related bivalent mechanism. MBTD1 competes with 53BP1 for the H4K20me2 mark, affecting its retention at the break cooperatively with H4 acetylation by TIP60. In addition, we show that H2AK15ub deposition by RNF168 inhibits chromatin acetylation by TIP60, whereas H2AK15 can also be acetylated by TIP60 in vivo, therefore blocking its ubiquitylation. Altogether, these results uncover an intricate mechanism orchestrated by the TIP60 complex to regulate 53BP1-dependent repair pathway selection, through incompatible bivalent binding/action on chromatin.
2016-04-30 | GSE69645 | GEO
Project description:Histone modifications play crucial roles in transcriptional activation, and aberrant epigenetic changes are associated with oncogenesis. Lysine (K) acetyltransferases 5 (TIP60, also known as KAT5) is reportedly implicated in cancer development and maintenance, although its function in lung cancer remains controversial. Here we demonstrate that TIP60 knockdown in non-small cell lung cancer cell lines decreased tumor cell growth, migration, and invasion. Furthermore, analysis of a mouse lung cancer model with lung-specific conditional Tip60 knockout revealed suppressed tumor formation relative to controls, but no apparent effects on normal lung homeostasis. RNA-seq and ChIP-seq analyses of inducible TIP60 knockdown H1975 cells relative to controls revealed transglutaminase enzyme (TGM5) as downstream of TIP60. Investigation of a connectivity map database identified several candidate compounds that decrease TIP60 mRNA, one that suppressed tumor growth in cell culture and in vivo. In addition, TH1834, a TIP60 acetyltransferase inhibitor, showed comparable antitumor effects in cell culture and in vivo. Taken together, suppression of TIP60 activity shows tumor-specific efficacy against lung cancer, with no overt effect on normal tissues. Our work suggests that targeting TIP60 could be a promising approach to treating lung cancer.
| S-EPMC10236639 | biostudies-literature
Project description:The Tip60 (also known as Kat5) lysine acetyltransferase functions broadly as a transcriptional co-activator that acetylates histones. In contrast, Tip60 functions in embryonic stem cells (ESCs) both to silence genes that promote differentiation and to activate genes required for proliferation. The mechanism by which Tip60 functions as a repressor is unknown. Here we show that the class II histone deacetylase Hdac6 co-purifies with Tip60-p400 complex from ESCs and is necessary for complete silencing of most differentiation genes targeted by Tip60. In contrast to differentiated cells, where Hdac6 is mainly cytoplasmic and does not interact with Tip60, Hdac6 is largely nuclear in ESCs and neural stem cells (NSCs) and interacts with Tip60-p400 in both cell types. Hdac6 is enriched at promoters bound by Tip60-p400 in ESCs, but while Tip60 binds on both sides of transcription start sites (TSSs), Hdac6 binding overlaps with only the downstream Tip60 peak. Surprisingly, Hdac6 does not deacetylate histones at these sites, but rather is required for Tip60 binding. These data suggest that nuclear exclusion of Hdac6 during differentiation plays a major role in modulation of Tip60-p400 function. We determined the genome-wide localization of Tip60 and Hdac6 in mouse ES cells, and examined genomic binding profiles of Tip60 and Hdac6 upon indicated knockdown by ChIP-seq. We examined genomic binding profiles of p400 upon indicated knockdown by ChIP-seq.
2013-11-20 | E-GEOD-42209 | biostudies-arrayexpress
Project description:The X-linked deubiquitinase, USP9X, is implicated in multiple cancers by targeting various substrates. Increased expression of USP9X is observed in non-small cell lung cancer (NSCLC) and is correlated with poor prognosis. However, the molecular mechanism for USP9X regulating tumor cell survival and tumorigenesis in NSCLC is less defined. In this study, chemical labeling quantitative proteomic screening was applied to analyze A549 cells with or without USP9X RNA interference, and the resulting data suggested that TTK is a potential substrate of USP9X. Further experimental evidences confirmed that USP9X stabilized TTK via direct interaction and deubiquitination of TTK. Moreover, knockdown of USP9X or TTK inhibited cell proliferation, migration and tumorigenesis, and the immunohistochemical analysis of clinical NSCLC samples showed that the protein expression levels of USP9X and TTK were significantly elevated and positively correlated in tumor tissues. In summary, our data demonstrated that the USP9X-TTK axis may play a critical role in NSCLC, and could be considered as the potential therapeutic target.
2018-05-07 | PXD007726 | Pride