Редактирование: HMGA2

High mobility group protein HMGI-C (High mobility group AT-hook protein 2) [HMGIC]

==Publications==

{{medline-entry
|title=4D Genome Rewiring during Oncogene-Induced and Replicative Senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32220303
|abstract=To understand the role of the extensive senescence-associated 3D genome reorganization, we generated genome-wide chromatin interaction maps, epigenome, replication-timing, whole-genome bisulfite sequencing, and gene expression profiles from cells entering replicative senescence (RS) or upon oncogene-induced senescence (OIS). We identify senescence-associated heterochromatin domains (SAHDs). Differential intra- versus inter-SAHD interactions lead to the formation of senescence-associated heterochromatin foci (SAHFs) in OIS but not in RS. This OIS-specific configuration brings active genes located in genomic regions adjacent to SAHDs in close spatial proximity and favors their expression. We also identify [[DNMT1]] as a factor that induces SAHFs by promoting [[HMGA2]] expression. Upon [[DNMT1]] depletion, OIS cells transition to a 3D genome conformation akin to that of cells in replicative senescence. These data show how multi-omics and imaging can identify critical features of RS and OIS and discover determinants of acute senescence and SAHF formation.
|mesh-terms=* Cells, Cultured
* Cellular Senescence
* Chromatin Assembly and Disassembly
* DNA (Cytosine-5-)-Methyltransferase 1
* DNA Methylation
* Fibroblasts
* Genome, Human
* Heterochromatin
* Humans
* In Situ Hybridization, Fluorescence
* Oncogenes
|keywords=* 3D genome architecture
* DNMT1
* Hi-C
* chromatin compartments
* gene regulation
* oncogene-induced senescence
* replicative senescence
* senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7208559
}}
{{medline-entry
|title=The protective effects of [[HMGA2]] in the senescence process of bone marrow-derived mesenchymal stromal cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32068957
|abstract=Bone marrow-derived mesenchymal stromal cells (MSCs) have been wildly applied to cell-based strategies for tissue engineering and regenerative medicine; however, they have to undergo the senescence process and thus appeared to be less therapeutic effective. [[HMGA2]], a protein belonged to high mobility group A (HMGA) family, exhibits an inverse expression level related to embryonic development and acts as a developmental regulator in stem cell self-renewal progression. Therefore, we performed senescence-associated β-galactosidase (SA-β-gal) staining, transwell assay, to examine the changes of MSCs in different stages and then over-expressed [[HMGA2]] in MSCs by lentivirus transfection. We found the percentage of SA-β-gal staining positive cells in MSCs from 24-month-old Sprague-Dawley (SD) rats (O-MSCs) was significantly higher compared with MSCs from 2-week-old SD rats (Y-MSCs), and the expression levels of P21 and P53, two senescence-related molecules, were also significantly up-regulated in O-MSCs than in Y-MSCs. In contrast, the [[HMGA2]] expression level in O-MSCs was dramatically down-regulated in contrast to Y-MSCs. In additional, the migration ability in O-MSCs was significantly attenuated than in Y-MSCs. After successfully over-expressed [[HMGA2]] in O-MSCs, the percentage of SA-β-gal staining positive cells and the expression levels of P21 and P53 were reduced, and the migration ability was improved compared with O-MSCs without treatment. Further, mRNA sequencing analysis revealed that overexpression of [[HMGA2]] changed the expression of genes related to cell proliferation and senescence, such as Lyz2, Pf4, Rgs2, and Mstn. Knockdown of Rgs2 in [[HMGA2]] overexpression O-MSCs could antagonize the protective effect of [[HMGA2]] in the senescence process of O-MSCs.

|keywords=* bone marrow derived mesenchymal stromal cells (MSCs)
* high-mobility group AT-hook 2 (HMGA2)
* regulator of G protein signaling 2 (Rgs2)
* senescence
|full-text-url=https://sci-hub.do/10.1002/term.3023
}}
{{medline-entry
|title=Epigallocatechin-3-gallate and BIX-01294 have different impact on epigenetics and senescence modulation in acute and chronic myeloid leukemia cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30194939
|abstract=Myeloid leukemia treatment is quite successful nowadays; nevertheless the development of new therapies is still necessary. In the present study, we investigated the potential of epigenetic modulators EGCG (epigallocatechin-3-gallate) and BIX-01294 (N-(1-benzylpiperidin-4-yl)-6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine) to alter epigenetic state and cause cellular senescence in acute and chronic myeloid leukemia NB4 and K562 cells. We have shown that after leukemia cell treatment with EGCG and BIX-01294 the proliferation and survival were inhibited of both cell lines; however, only NB4 cells underwent apoptosis. Both epigenetic modulators caused cell cycle arrest in G0/G1 phase as assessed by RT-qPCR (p53, p21, Rb) and flow cytometry analysis. Increased levels of [[ATM]], [[HMGA2]], phosphorylated [[ATM]], and SA-β-galactosidase staining indicated that EGCG caused cellular senescence, whereas BIX-01294 did not. Immunoblot analysis of epigenetic players [[DNMT1]], HP1α, H3K9me3, [[EZH2]], and [[SUZ12]] demonstrated beneficial epigenetic modulation by both agents with exception of mainly no epigenetic changes caused in K562 cells by EGCG. Therefore, we suggest EGCG as a promising epigenetic modulator for acute promyelocytic leukemia therapy and as a potential cellular senescence inducer in both acute and chronic myeloid leukemia treatment, whereas BIX-01294 could be beneficial as an epigenetic modifier for both myeloid leukemias treatment.
|mesh-terms=* Antineoplastic Agents
* Azepines
* Catechin
* Cellular Senescence
* Drug Screening Assays, Antitumor
* Epigenesis, Genetic
* G1 Phase Cell Cycle Checkpoints
* Gene Expression Regulation, Neoplastic
* Humans
* K562 Cells
* Leukemia, Myelogenous, Chronic, BCR-ABL Positive
* Leukemia, Promyelocytic, Acute
* Quinazolines
|keywords=* BIX-01294
* EGCG
* Epigenetic regulation
* Myeloid leukemia
* Senescence
|full-text-url=https://sci-hub.do/10.1016/j.ejphar.2018.09.005
}}
{{medline-entry
|title=Molecular differences between stromal cell populations from deciduous and permanent human teeth.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25927523
|abstract=Deciduous and permanent human teeth represent an excellent model system to study aging of stromal populations. Aging is tightly connected to self-renewal and proliferation and thus, mapping potential molecular differences in these characteristics between populations constitutes an important task. Using specifically designed microarray panels, Real-Time Quantitative Polymerase Chain Reaction (RT q-PCR), Western blot, immunohistochemistry and siRNA-mediated knock down experiments, we have detected a number of molecules that were differentially expressed in dental pulp from deciduous and permanent teeth extracted from young children and adults, respectively. Among the differentially regulated genes, high-mobility group AT-hook 2 ([[HMGA2]]), a stem cell-associated marker, stood out as a remarkable example with a robust expression in deciduous pulp cells. siRNA-mediated knock down of [[HMGA2]] expression in cultured deciduous pulp cells caused a down-regulated expression of the pluripotency marker [[NANOG]]. This finding indicates that [[HMGA2]] is a pulpal stem cell regulatory factor. In addition to this, we discovered that several proliferation-related genes, including CDC2A and [[CDK4]], were up-regulated in deciduous pulp cells, while matrix genes [[COL1A1]], fibronectin and several signaling molecules, such as VEGF, FGFr-1 and IGFr-1 were up-regulated in the pulp cells from permanent teeth. Taken together, our data suggest that deciduous pulp cells are more robust in self- renewal and proliferation, whereas adult dental pulp cells are more capable of signaling and matrix synthesis.
|mesh-terms=* Adult
* Aging
* CDC2 Protein Kinase
* Cell Proliferation
* Cells, Cultured
* Child
* Child, Preschool
* Cyclin-Dependent Kinase 4
* Cyclin-Dependent Kinases
* Dental Pulp
* Down-Regulation
* HMGA2 Protein
* Homeodomain Proteins
* Humans
* Middle Aged
* Nanog Homeobox Protein
* Oligonucleotide Array Sequence Analysis
* RNA Interference
* RNA, Small Interfering
* Stromal Cells
* Tooth, Deciduous
* Young Adult

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417277
}}
{{medline-entry
|title=Rb protein is essential to the senescence-associated heterochromatic foci formation induced by [[HMGA2]] in primary WI38 cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23969248
|abstract=Cellular senescence is an irreversible form of cell cycle arrest that provides a barrier to neoplastic transformation. The integrity of the Rb (Retinoblastoma) pathway is necessary for the formation of the senescence-associated heterochromatin foci (SAHF) that offers a molecular basis for the stability of the senescent state. Surprisingly, although high mobility group A2 protein ([[HMGA2]]) can promote tumorigenesis and inhibit Rb function in tumor cells, high-level expression of [[HMGA2]] is sufficient to induce SAHF formation in primary cells. It therefore becomes significant to determine whether Rb protein is necessary in [[HMGA2]]-induced SAHF formation. In this study, we established the cellular senescence and SAHF assembly WI38 cell model by ectopic expression of [[HMGA2]], in which typical senescent markers were seen, including notable upregulation of p53, p21 and p16, and elevated SA-β-galactosidase staining together with downregulation of E2F target genes. We then showed that the Rb pathway inhibitor E7 protein was able to partly abolish the ability of SAHF formation after [[HMGA2]] expression in WI38 cells, indicating that Rb is a crucial factor for [[HMGA2]]-induced SAHF formation. However, Rb depletion did not completely rescue the cell growth arrest induced by [[HMGA2]], suggesting that Rb is not an exclusive pathway for [[HMGA2]]-induced senescence in WI38 cells. 
|mesh-terms=* Aging
* Cell Cycle
* Cell Line, Tumor
* Cellular Senescence
* Gene Expression Regulation, Neoplastic
* HMGA2 Protein
* Heterochromatin
* Humans
* Neoplasms
* Retinoblastoma Protein
|keywords=* Cellular senescence
* HMGA2
* Rb
* SAHF
|full-text-url=https://sci-hub.do/10.1016/j.jgg.2013.05.007
}}
{{medline-entry
|title=MYCN/[[LIN28B]]/Let-7/[[HMGA2]] pathway implicated by meta-analysis of GWAS in suppression of post-natal proliferation thereby potentially contributing to aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23639551
|abstract=Mammalian organ and body growth slows and finally terminates because of a progressive suppression of cell proliferation, however little is known about the genetic regulatory mechanisms responsible. A meta-analysis of genome-wide association studies using growth and development-related traits revealed that two genes, [[HMGA2]] and [[LIN28B]], had multiple associations. Altered [[HMGA2]] expression has been shown to result in both overgrowth and pygmy phenotypes in mice and overgrowth in humans. These genes are members of the MYCN/[[LIN28B]]/Let-7/[[HMGA2]] pathway and homologs of [[LIN28B]] and let-7 are known to regulate developmental timing in Caenorhabditis elegans. Strikingly, expression levels of let-7 and Hmga2 in murine stem cells continue to increase and decrease, respectively, after growth terminates, suggesting that this pathway may contribute to regulating the pace of both development and age-related degenerative phenotypes. 
|mesh-terms=* Aging
* Animals
* Caenorhabditis elegans
* Caenorhabditis elegans Proteins
* DNA-Binding Proteins
* Female
* Gene Expression Regulation
* Genome-Wide Association Study
* HMGA2 Protein
* Humans
* Male
* Meta-Analysis as Topic
* Mice
* MicroRNAs
* N-Myc Proto-Oncogene Protein
* Nuclear Proteins
* Oncogene Proteins
* Proto-Oncogene Proteins
* RNA-Binding Proteins

|full-text-url=https://sci-hub.do/10.1016/j.mad.2013.04.006
}}