A5013065571- Genomics, phytochemicals, and oxidative stress
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- RNA regulation and disease
- MicroRNA in disease regulation
- Genetic factors in colorectal cancer
- interferon and immune responses
- RNA Research and Splicing
- Plant Virus Research Studies
- Colorectal Cancer Screening and Detection
- Genomics and Chromatin Dynamics
- PI3K/AKT/mTOR signaling in cancer
- Cancer-related Molecular Pathways
- Molecular Biology Techniques and Applications
- Cancer Genomics and Diagnostics
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
Moffitt Cancer Center
2020-2024
Molecular Oncology (United States)
2020-2024
Abstract The most frequent genetic alterations across multiple human cancers are mutations in TP53 and the activation of PI3K/AKT pathway, two events crucial for cancer progression. Mutations lead to inhibition tumour metastasis suppressor TAp63 , a p53 family member. By performing mouse-human cross species analysis between metastatic mammary adenocarcinoma mouse model models breast progression, we identified TAp63-regulated oncogenic lncRNAs, TROLL-2 TROLL-3 . Further, using pan-cancer...
The p53 family member TP63 encodes two sets of N-terminal isoforms, TAp63 and ΔNp63 isoforms. They each regulate diverse biological functions in epidermal morphogenesis cancer. In the skin, where their activities have been extensively characterized, prevents premature aging by regulating quiescence genomic stability stem cells required for wound healing hair regeneration, while controls maintenance terminal differentiation basal cells. This functional diversity is surprising given that these...
<div>Abstract<p>The p53 family member <i>TP63</i> encodes two sets of N-terminal isoforms, TAp63 and ΔNp63 isoforms. They each regulate diverse biological functions in epidermal morphogenesis cancer. In the skin, where their activities have been extensively characterized, prevents premature aging by regulating quiescence genomic stability stem cells required for wound healing hair regeneration, while controls maintenance terminal differentiation basal cells. This...
<div>Abstract<p>The p53 family member <i>TP63</i> encodes two sets of N-terminal isoforms, TAp63 and ΔNp63 isoforms. They each regulate diverse biological functions in epidermal morphogenesis cancer. In the skin, where their activities have been extensively characterized, prevents premature aging by regulating quiescence genomic stability stem cells required for wound healing hair regeneration, while controls maintenance terminal differentiation basal cells. This...
<p>Identification of ∆Np63 and TAp63 regulated transcriptomes. <b>A,</b> Unsupervised clustering the transcriptional profiles in WT, <i>ΔNp63<sup>−</sup><sup>/</sup><sup>−</sup></i>, <i>TAp63<sup>−</sup><sup>/</sup><sup>−</sup></i> epidermal cells using Pearson correlation coefficient (PCC). <b>B,</b> Heat map visualization genes affected either...
<p>Endogenous ∆Np63 and TAp63 bind to distinct regions throughout the genome. <b>A,</b> Experimental outline. WT, <i>ΔNp63<sup>−</sup><sup>/</sup><sup>−</sup></i>, <i>TAp63<sup>−</sup><sup>/</sup><sup>−</sup></i> epidermal cells were isolated from embryonic day 18.5 (E18.5) embryos. RNA extracted these was used for expression profiling by RNA-seq, chromatin genome-wide analysis...
<p>Identification of ∆Np63 and TAp63 regulated transcriptomes. <b>A,</b> Unsupervised clustering the transcriptional profiles in WT, <i>ΔNp63<sup>−</sup><sup>/</sup><sup>−</sup></i>, <i>TAp63<sup>−</sup><sup>/</sup><sup>−</sup></i> epidermal cells using Pearson correlation coefficient (PCC). <b>B,</b> Heat map visualization genes affected either...
<p>∆Np63 cooperates with the FOX family members to regulate cell motility genes</p>
<p>List of differentially expressed genes in ΔNp63+/+ vs. ΔNp63-/- cells (mouse epidermal, lung basal, and mammary epithelial cells) or TAp63+/+ TAp63-/- epidermal cells).</p>
<p>List of differentially expressed genes in ΔNp63+/+ vs. ΔNp63-/- cells (mouse epidermal, lung basal, and mammary epithelial cells) or TAp63+/+ TAp63-/- epidermal cells).</p>
<p>∆Np63 and TAp63 control the expression of their common target genes together with Stat proteins. <b>A,</b> qRT-PCR for indicated ΔNp63 in epidermal cells genotype. Data are mean ± SD, <i>n</i> = 3, * versus WT, <i>P <</i> 0.005, two-tailed <i>t</i> test. <b>B,</b> ∆Np63 ChIP assays using genotype on peaks genes. <b>C,</b> same genomic regions as B. <b>D,</b> Stat4 ChIP-re-ChIP chromatin...
<p>List of DNA oligonucleotides for the TAp63 and ∆Np63 ChIP assays</p>
<p>List of transcriptional factor motifs differentially enriched in the 3 groups TAp63-specific direct target genes, ∆Np63-specific and common genes. For analysis transcription only 2 kb regions surrounding p63 peaks each genes were considered.</p>
<p>TAp63 and NRF2 coordinately regulate the expression of TAp63-specific target genes</p>
<p>List of identified metabolites detected via liquid chromatography-high resolution mass spectrometry in TAp63-/- vs. WT mouse epidermal cells.</p>
<p>List of identified metabolites detected via liquid chromatography-high resolution mass spectrometry in TAp63-/- vs. WT mouse epidermal cells.</p>
<p>List of the siRNA sequences.</p>
<p>List of genes differentially expressed between TAp63-/- or ΔNp63-/- mouse epidermal cells and the WT cells. For each gene, count TAp63 ∆Np63 bound peaks within 10 kb from gene bodies is indicated.</p>
<p>∆Np63 cooperates with the FOX family members to regulate cell motility genes</p>
<p>Endogenous ∆Np63 and TAp63 bind to distinct regions throughout the genome. <b>A,</b> Experimental outline. WT, <i>ΔNp63<sup>−</sup><sup>/</sup><sup>−</sup></i>, <i>TAp63<sup>−</sup><sup>/</sup><sup>−</sup></i> epidermal cells were isolated from embryonic day 18.5 (E18.5) embryos. RNA extracted these was used for expression profiling by RNA-seq, chromatin genome-wide analysis...
<p>∆Np63 and TAp63 control distinct biological processes by cooperating with different transcription factors. <b>A,</b> Venn diagrams of ΔNp63-specific, common, TAp63-specific direct target genes, p63 ChIP-seq peaks ± 10 kb from their genomic loci. <b>B–D,</b> List the differentially enriched pathways in genes. <b>E,</b> Table listing top motifs Highlighted yellow are factors selected for validation.</p>
<p>List of DNA oligonucleotides to assess the expression levels TAp63 and ∆Np63 target genes.</p>
<p>TAp63 and NRF2 coordinately regulate the expression of TAp63-specific target genes. <b>A,</b> qRT-PCR for indicated genes in epidermal cells genotype. Data are mean ± SD, <i>n</i> = 3, * versus WT, <i>P <</i> 0.005, two-tailed <i>t</i> test. <b>B,</b> TAp63 ChIP assays using genotype on peaks <b>C,</b> Nrf2 ChIP-re-ChIP chromatin immunoprecipitated genomic regions from 3. <b>D,</b>...
<p>List of DNA oligonucleotides to assess the expression levels TAp63 and ∆Np63 target genes.</p>