The expression of p53-target genes in the hypoxia-tolerant subterranean mole-rat is hypoxia-dependent and similar to expression patterns in solid tumors

Epigenetic modifications play significant roles in adaptive evolution. The tumor suppressor p53, well known for controlling cell fate and maintaining genomic stability, is much less known as a master gene in environmental adaptation involving methylation modifications. The blind subterranean mole rat Spalax eherenbergi superspecies in Israel consists of four species that speciated peripatrically. Remarkably, the northern Galilee species Spalax galili (2n = 52) underwent adaptive ecological sympatric speciation, caused by the sharply divergent chalk and basalt ecologies. This was demonstrated by mitochondrial and nuclear genomic evidence. Here we show that the expression patterns of the p53 regulatory pathway diversified between the abutting sympatric populations of S. galili in sharply divergent chalk–basalt ecologies. We identified higher methylation on several sites of the p53 promoter in the population living in chalk soil (chalk population). Site mutagenesis showed that methylation on these sites linked to the transcriptional repression of p53 involving Cut-Like Homeobox 1 (Cux1), paired box 4 (Pax 4), Pax 6, and activator protein 1 (AP-1). Diverse expression levels of p53 between the incipiently sympatrically speciating chalk–basalt abutting populations of S. galili selectively affected cell-cycle arrest but not apoptosis. We hypothesize that methylation modification of p53 has adaptively shifted in supervising its target genes during sympatric speciation of S. galili to cope with the contrasting environmental stresses of the abutting divergent chalk–basalt ecologies.

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381: Promoter Hypermethylation Profile of Kidney Cancer with New Pro-Apoptotic P53 Target Genes and Possible Clinical Implications

The Journal of Urology ◽

10.1016/s0022-5347(18)32637-5 ◽

2006 ◽

Vol 175 (4S) ◽

pp. 125-125

Author(s):

Frank Christoph ◽

Steffen Weikert ◽

Carsten Kempkensteffen ◽

Martin Schostak ◽

Hans Krause ◽

...

Keyword(s):

Kidney Cancer ◽

Target Genes ◽

Promoter Hypermethylation ◽

Clinical Implications ◽

P53 Target Genes

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Differential Activation of p53 Target Genes in Breast Cancer

10.21236/ada405348 ◽

2002 ◽

Author(s):

Edward Thornborrow ◽

James Manfredi

Keyword(s):

Breast Cancer ◽

Target Genes ◽

Differential Activation ◽

P53 Target Genes

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Histone deacetylase (HDAC) 9: versatile biological functions and emerging roles in human cancer

Cellular Oncology ◽

10.1007/s13402-021-00626-9 ◽

2021 ◽

Author(s):

Chun Yang ◽

Stéphane Croteau ◽

Pierre Hardy

Keyword(s):

Histone Deacetylase ◽

Posttranslational Modifications ◽

Histone Deacetylases ◽

Muscle Development ◽

Target Genes ◽

Human Cancer ◽

Expression Patterns ◽

Aberrant Expression ◽

Physiological Processes ◽

Cancer Pathogenesis

Abstract Background HDAC9 (histone deacetylase 9) belongs to the class IIa family of histone deacetylases. This enzyme can shuttle freely between the nucleus and cytoplasm and promotes tissue-specific transcriptional regulation by interacting with histone and non-histone substrates. HDAC9 plays an essential role in diverse physiological processes including cardiac muscle development, bone formation, adipocyte differentiation and innate immunity. HDAC9 inhibition or activation is therefore a promising avenue for therapeutic intervention in several diseases. HDAC9 overexpression is also common in cancer cells, where HDAC9 alters the expression and activity of numerous relevant proteins involved in carcinogenesis. Conclusions This review summarizes the most recent discoveries regarding HDAC9 as a crucial regulator of specific physiological systems and, more importantly, highlights the diverse spectrum of HDAC9-mediated posttranslational modifications and their contributions to cancer pathogenesis. HDAC9 is a potential novel therapeutic target, and the restoration of aberrant expression patterns observed among HDAC9 target genes and their related signaling pathways may provide opportunities to the design of novel anticancer therapeutic strategies.

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Genome-wide analysis of changes in miRNA and target gene expression reveals key roles in heterosis for Chinese cabbage biomass

Horticulture Research ◽

10.1038/s41438-021-00474-6 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Peirong Li ◽

Tongbing Su ◽

Deshuang Zhang ◽

Weihong Wang ◽

Xiaoyun Xin ◽

...

Keyword(s):

Chinese Cabbage ◽

Leaf Development ◽

Target Genes ◽

Expression Patterns ◽

Seedling Stage ◽

Differentially Expressed ◽

Small Rna Sequencing ◽

Leaf Morphogenesis ◽

Expression Levels ◽

Parental Lines

AbstractHeterosis is a complex phenomenon in which hybrids show better phenotypic characteristics than their parents do. Chinese cabbage (Brassica rapa L. spp. pekinensis) is a popular leafy crop species, hybrids of which are widely used in commercial production; however, the molecular basis of heterosis for biomass of Chinese cabbage is poorly understood. We characterized heterosis in a Chinese cabbage F1 hybrid cultivar and its parental lines from the seedling stage to the heading stage; marked heterosis of leaf weight and biomass yield were observed. Small RNA sequencing revealed 63 and 50 differentially expressed microRNAs (DEMs) at the seedling and early-heading stages, respectively. The expression levels of the majority of miRNA clusters in the F1 hybrid were lower than the mid-parent values (MPVs). Using degradome sequencing, we identified 1,819 miRNA target genes. Gene ontology (GO) analyses demonstrated that the target genes of the MPV-DEMs and low parental expression level dominance (ELD) miRNAs were significantly enriched in leaf morphogenesis, leaf development, and leaf shaping. Transcriptome analysis revealed that the expression levels of photosynthesis and chlorophyll synthesis-related MPV-DEGs (differentially expressed genes) were significantly different in the F1 hybrid compared to the parental lines, resulting in increased photosynthesis capacity and chlorophyll content in the former. Furthermore, expression of genes known to regulate leaf development was also observed at the seedling stage. Arabidopsis plants overexpressing BrGRF4.2 and bra-miR396 presented increased and decreased leaf sizes, respectively. These results provide new insight into the regulation of target genes and miRNA expression patterns in leaf size and heterosis for biomass of B. rapa.

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Circular RNA circSDHC serves as a sponge for miR-127-3p to promote the proliferation and metastasis of renal cell carcinoma via the CDKN3/E2F1 axis

Molecular Cancer ◽

10.1186/s12943-021-01314-w ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Junjie Cen ◽

Yanping Liang ◽

Yong Huang ◽

Yihui Pan ◽

Guannan Shu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Target Genes ◽

Expression Patterns ◽

Luciferase Reporter ◽

Circular Rnas ◽

Proliferation And Metastasis

Abstract Background There is increasing evidence that circular RNAs (circRNAs) have significant regulatory roles in cancer development and progression; however, the expression patterns and biological functions of circRNAs in renal cell carcinoma (RCC) remain largely elusive. Method Bioinformatics methods were applied to screen for circRNAs differentially expressed in RCC. Analysis of online circRNAs microarray datasets and our own patient cohort indicated that circSDHC (hsa_circ_0015004) had a potential oncogenic role in RCC. Subsequently, circSDHC expression was measured in RCC tissues and cell lines by qPCR assay, and the prognostic value of circSDHC evaluated. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of circSDHC on RCC proliferation and metastasis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between circSDHC, miR-127-3p and its target genes. Results Clinically, high circSDHC expression was correlated with advanced TNM stage and poor survival in patients with RCC. Further, circSDHC promoted tumor cell proliferation and invasion, both in vivo and in vitro. Analysis of the mechanism underlying the effects of circSDHC in RCC demonstrated that it binds competitively to miR-127-3p and prevents its suppression of a downstream gene, CDKN3, and the E2F1 pathway, thereby leading to RCC malignant progression. Furthermore, knockdown of circSDHC caused decreased CDKN3 expression and E2F1 pathway inhibition, which could be rescued by treatment with an miR-127-3p inhibitor. Conclusion Our data indicates, for the first time, an essential role for the circSDHC/miR-127-3p/CDKN3/E2F1 axis in RCC progression. Thus, circSDHC has potential to be a new therapeutic target in patients with RCC.

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Organization of the circadian system in the subterranean mole rat, Cryptomys hottentotus (Bathyergidae)

Brain Research ◽

10.1016/s0006-8993(02)04208-7 ◽

2003 ◽

Vol 967 (1-2) ◽

pp. 48-62 ◽

Cited By ~ 24

Author(s):

Julia Negroni ◽

Nickel C Bennett ◽

Howard M Cooper

Keyword(s):

Circadian System ◽

Mole Rat ◽

Subterranean Mole Rat

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Genetic and epigenetic concept of SARS-CoV-2 targets in different renal cancer subtypes

Turkish Journal of Biochemistry ◽

10.1515/tjb-2020-0233 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Dilara Fatma Akin-Bali ◽

Rahşan Ilikci Sagkan

Keyword(s):

Renal Cancer ◽

Promoter Methylation ◽

Target Genes ◽

Expression Patterns ◽

Rna Expression ◽

Total Rate ◽

Cancer Subtypes ◽

Genetic Landscape ◽

Healthy Control ◽

Genetic Anomaly

AbstractObjectivesRecent advances in defining the genetic landscape of has shown the host cell- SARS-CoV-2 interaction via ACE2 protein and the presence of at least three additional virus invasion genes including TMPRSS2, FURIN, CD147/BSG. In current study, we investigated the mutation and m-RNA expression patterns of target genes by evaluating the associations between genetic and epigenetic mechanisms in the target genes and susceptibility of SARS-CoV-2 infection of renal cancer subtypes.MethodsWe investigated the mutation and m-RNA expression patterns of our target genes. The promoter methylation profiles of target genes were tested in the UALCAN database.ResultsThe total rate of carrying genetic anomaly in the target genes including was 1.6% and seven mutations, one of which had a pathogenic feature, were detected. The expression analysis results in renal cancer groups showed that while the KIRC and KIRP patients had a lower level of TMPRSS2 than the healthy control, their ACE2 level was high. KICH patients had a higher level of CD147/BSG expression than the healthy group. The promoter methylation levels of ACE2 in KIRC and KIRP were reduced.ConclusionsWe concluded that renal cancer patients may be more sensitive to SARS-CoV-2 infection, which may worsen the prognosis.

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Birdsong Decreases Protein Levels of FoxP2, a Molecule Required for Human Speech

Journal of Neurophysiology ◽

10.1152/jn.90415.2008 ◽

2008 ◽

Vol 100 (4) ◽

pp. 2015-2025 ◽

Cited By ~ 58

Author(s):

Julie E. Miller ◽

Elizabeth Spiteri ◽

Michael C. Condro ◽

Ryan T. Dosumu-Johnson ◽

Daniel H. Geschwind ◽

...

Keyword(s):

Mrna Expression ◽

Target Genes ◽

Expression Patterns ◽

Vocal Learning ◽

Brain Regions ◽

Motor Deficits ◽

Mrna Levels ◽

Adult Males ◽

Protein Levels ◽

Area X

Cognitive and motor deficits associated with language and speech are seen in humans harboring FOXP2 mutations. The neural bases for FOXP2 mutation-related deficits are thought to reside in structural abnormalities distributed across systems important for language and motor learning including the cerebral cortex, basal ganglia, and cerebellum. In these brain regions, our prior research showed that FoxP2 mRNA expression patterns are strikingly similar between developing humans and songbirds. Within the songbird brain, this pattern persists throughout life and includes the striatal subregion, Area X, that is dedicated to song development and maintenance. The persistent mRNA expression suggests a role for FoxP2 that extends beyond the formation of vocal learning circuits to their ongoing use. Because FoxP2 is a transcription factor, a role in shaping circuits likely depends on FoxP2 protein levels which might not always parallel mRNA levels. Indeed our current study shows that FoxP2 protein, like its mRNA, is acutely downregulated in mature Area X when adult males sing with some differences. Total corticosterone levels associated with the different behavioral contexts did not vary, indicating that differences in FoxP2 levels are not likely attributable to stress. Our data, together with recent reports on FoxP2's target genes, suggest that lowered FoxP2 levels may allow for expression of genes important for circuit modification and thus vocal variability.

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