• Je něco špatně v tomto záznamu ?

Loss of macroH2A1 decreases mitochondrial metabolism and reduces the aggressiveness of uveal melanoma cells

S. Giallongo, M. Di Rosa, R. Caltabiano, L. Longhitano, M. Reibaldi, A. Distefano, O. Lo Re, AM. Amorini, L. Puzzo, L. Salvatorelli, S. Palmucci, D. Tibullo, A. Russo, A. Longo, G. Lazzarino, G. Li Volti, M. Vinciguerra

. 2020 ; 12 (10) : 9745-9760. [pub] 20200512

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc21012593

Uveal melanoma (UM) is the most common primary intraocular tumour in adults. The most accurate prognostic factor of UM is classification by gene expression profiling. Currently, the role of epigenetics is much less defined compared to genetic mechanisms. We recently showed a strong prognostic role of the expression levels of histone variant macroH2A1 in UM patients. Here, we assessed the mechanistic effects of macroH2A1 on UM progression.UM cell lines were stably knocked down (KD) for macroH2A1, and proliferation and colony formation capacity were evaluated. Mitochondrial function was assayed through qPCR and HPLC analyses. Correlation between mitochondrial gene expression and cancer aggressiveness was studied using a bioinformatics approach.MacroH2A1 loss significantly attenuated UM cells proliferation and aggressiveness. Furthermore, genes involved in oxidative phosphorylation displayed a decreased expression in KD cells. Consistently, macroH2A1 loss resulted also in a significant decrease of mitochondrial transcription factor A (TFAM) expression, suggesting impaired mitochondrial replication. Bioinformatics analyses uncovered that the expression of genes involved in mitochondrial metabolism correlates with macroH2A1 and with cancer aggressiveness in UM patients. Altogether, our results suggest that macroH2A1 controls UM cells progression and it may represent a molecular target to develop new pharmacological strategies for UM treatment.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc21012593
003      
CZ-PrNML
005      
20210507101540.0
007      
ta
008      
210420s2020 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.18632/aging.103241 $2 doi
035    __
$a (PubMed)32401230
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Giallongo, Sebastiano $u Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy $u Center for Translational Medicine (CTM), International Clinical Research Center (FNUSA-ICRC), St Anne's University Hospital, Brno, Czech Republic $u Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
245    10
$a Loss of macroH2A1 decreases mitochondrial metabolism and reduces the aggressiveness of uveal melanoma cells / $c S. Giallongo, M. Di Rosa, R. Caltabiano, L. Longhitano, M. Reibaldi, A. Distefano, O. Lo Re, AM. Amorini, L. Puzzo, L. Salvatorelli, S. Palmucci, D. Tibullo, A. Russo, A. Longo, G. Lazzarino, G. Li Volti, M. Vinciguerra
520    9_
$a Uveal melanoma (UM) is the most common primary intraocular tumour in adults. The most accurate prognostic factor of UM is classification by gene expression profiling. Currently, the role of epigenetics is much less defined compared to genetic mechanisms. We recently showed a strong prognostic role of the expression levels of histone variant macroH2A1 in UM patients. Here, we assessed the mechanistic effects of macroH2A1 on UM progression.UM cell lines were stably knocked down (KD) for macroH2A1, and proliferation and colony formation capacity were evaluated. Mitochondrial function was assayed through qPCR and HPLC analyses. Correlation between mitochondrial gene expression and cancer aggressiveness was studied using a bioinformatics approach.MacroH2A1 loss significantly attenuated UM cells proliferation and aggressiveness. Furthermore, genes involved in oxidative phosphorylation displayed a decreased expression in KD cells. Consistently, macroH2A1 loss resulted also in a significant decrease of mitochondrial transcription factor A (TFAM) expression, suggesting impaired mitochondrial replication. Bioinformatics analyses uncovered that the expression of genes involved in mitochondrial metabolism correlates with macroH2A1 and with cancer aggressiveness in UM patients. Altogether, our results suggest that macroH2A1 controls UM cells progression and it may represent a molecular target to develop new pharmacological strategies for UM treatment.
650    _2
$a nádorové buněčné linie $7 D045744
650    _2
$a proliferace buněk $x genetika $7 D049109
650    _2
$a DNA vazebné proteiny $x metabolismus $7 D004268
650    _2
$a regulace genové exprese u nádorů $x genetika $7 D015972
650    _2
$a histony $x nedostatek $7 D006657
650    _2
$a lidé $7 D006801
650    _2
$a melanocyty $x metabolismus $7 D008544
650    _2
$a melanom $x genetika $7 D008545
650    _2
$a mitochondrie $x metabolismus $7 D008928
650    _2
$a mitochondriální proteiny $x metabolismus $7 D024101
650    _2
$a nádorové kmenové buňky $x metabolismus $7 D014411
650    _2
$a transkripční faktory $x metabolismus $7 D014157
650    _2
$a nádory uvey $x genetika $7 D014604
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Di Rosa, Michelino $u Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
700    1_
$a Caltabiano, Rosario $u Department G.F. Ingrassia, Section of Anatomic Pathology, University of Catania, Catania, Italy
700    1_
$a Longhitano, Lucia $u Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
700    1_
$a Reibaldi, Michele $u Department of Ophthalmology, University of Catania, Catania, Italy
700    1_
$a Distefano, Alfio $u Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
700    1_
$a Lo Re, Oriana $u Center for Translational Medicine (CTM), International Clinical Research Center (FNUSA-ICRC), St Anne's University Hospital, Brno, Czech Republic $u Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
700    1_
$a Amorini, Angela Maria $u Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
700    1_
$a Puzzo, Lidia $u Department G.F. Ingrassia, Section of Anatomic Pathology, University of Catania, Catania, Italy
700    1_
$a Salvatorelli, Lucia $u Department G.F. Ingrassia, Section of Anatomic Pathology, University of Catania, Catania, Italy
700    1_
$a Palmucci, Stefano $u Department of Ophthalmology, University of Catania, Catania, Italy
700    1_
$a Tibullo, Daniele $u Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
700    1_
$a Russo, Andrea $u Department of Ophthalmology, University of Catania, Catania, Italy
700    1_
$a Longo, Antonio $u Department of Ophthalmology, University of Catania, Catania, Italy
700    1_
$a Lazzarino, Giacomo $u UniCamillus-Saint Camillus International University of Health Sciences, Rome, Italy
700    1_
$a Li Volti, Giovanni $u Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy $u EuroMediterranean Institute of Science and Technology, Palermo, Italy
700    1_
$a Vinciguerra, Manlio $u Center for Translational Medicine (CTM), International Clinical Research Center (FNUSA-ICRC), St Anne's University Hospital, Brno, Czech Republic
773    0_
$w MED00172417 $t Aging $x 1945-4589 $g Roč. 12, č. 10 (2020), s. 9745-9760
856    41
$u https://pubmed.ncbi.nlm.nih.gov/32401230 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20210420 $b ABA008
991    __
$a 20210507101540 $b ABA008
999    __
$a ok $b bmc $g 1650872 $s 1132972
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2020 $b 12 $c 10 $d 9745-9760 $e 20200512 $i 1945-4589 $m Aging (Albany, NY. Online) $n Aging $x MED00172417
LZP    __
$a Pubmed-20210420

Najít záznam

Citační ukazatele

Možnosti archivace