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

J 2020

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

GIALLONGO, Sebastiano, M. DI ROSA, R. CALTABIANO, L. LONGHITANO, M. REIBALDI et. al.

Základní údaje

Originální název

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

Autoři

GIALLONGO, Sebastiano (380 Itálie, domácí), M. DI ROSA (380 Itálie), R. CALTABIANO (380 Itálie), L. LONGHITANO (380 Itálie), M. REIBALDI (380 Itálie), A. DISTEFANO (380 Itálie), Oriana LO RE (380 Itálie, domácí), A. M. AMORINI (380 Itálie), L. PUZZO (380 Itálie), L. SALVATORELLI (380 Itálie), S. PALMUCCI (380 Itálie), D. TIBULLO (380 Itálie), A. RUSSO (380 Itálie), A. LONGO (380 Itálie), G. LAZZARINO (380 Itálie), G. LI VOLTI (380 Itálie) a Manlio VINCIGUERRA (380 Itálie, garant)

Vydání

AGING-US, ORCHARD PARK, IMPACT JOURNALS LLC, 2020, 1945-4589

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.682

Kód RIV

RIV/00216224:14110/20:00116011

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.18632/aging.103241

UT WoS

000537718700058

Klíčová slova anglicky

macroH2A1; histones; uveal melanoma; metabolism; epigenetics

Štítky

14110513, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 16. 7. 2020 12:49, Mgr. Tereza Miškechová

Anotace

V originále

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.

Citovat

GIALLONGO, Sebastiano, M. DI ROSA, R. CALTABIANO, L. LONGHITANO, M. REIBALDI, A. DISTEFANO, Oriana LO RE, A. M. AMORINI, L. PUZZO, L. SALVATORELLI, S. PALMUCCI, D. TIBULLO, A. RUSSO, A. LONGO, G. LAZZARINO, G. LI VOLTI a Manlio VINCIGUERRA. Loss of macroH2A1 decreases mitochondrial metabolism and reduces the aggressiveness of uveal melanoma cells. AGING-US. ORCHARD PARK: IMPACT JOURNALS LLC, 2020, roč. 12, č. 10, s. 9745-9760. ISSN 1945-4589. Dostupné z: https://dx.doi.org/10.18632/aging.103241.

@article{1670498,
   author = {Giallongo, Sebastiano and Di Rosa, M. and Caltabiano, R. and Longhitano, L. and Reibaldi, M. and Distefano, A. and Lo Re, Oriana and Amorini, A. M. and Puzzo, L. and Salvatorelli, L. and Palmucci, S. and Tibullo, D. and Russo, A. and Longo, A. and Lazzarino, G. and Li Volti, G. and Vinciguerra, Manlio},
   article_location = {ORCHARD PARK},
   article_number = {10},
   doi = {http://dx.doi.org/10.18632/aging.103241},
   keywords = {macroH2A1; histones; uveal melanoma; metabolism; epigenetics},
   language = {eng},
   issn = {1945-4589},
   journal = {AGING-US},
   title = {Loss of macroH2A1 decreases mitochondrial metabolism and reduces the aggressiveness of uveal melanoma cells},
   url = {https://europepmc.org/article/med/32401230},
   volume = {12},
   year = {2020}
}

TY  - JOUR
ID  - 1670498
AU  - Giallongo, Sebastiano - Di Rosa, M. - Caltabiano, R. - Longhitano, L. - Reibaldi, M. - Distefano, A. - Lo Re, Oriana - Amorini, A. M. - Puzzo, L. - Salvatorelli, L. - Palmucci, S. - Tibullo, D. - Russo, A. - Longo, A. - Lazzarino, G. - Li Volti, G. - Vinciguerra, Manlio
PY  - 2020
TI  - Loss of macroH2A1 decreases mitochondrial metabolism and reduces the aggressiveness of uveal melanoma cells
JF  - AGING-US
VL  - 12
IS  - 10
SP  - 9745-9760
EP  - 9745-9760
PB  - IMPACT JOURNALS LLC
SN  - 19454589
KW  - macroH2A1
KW  - histones
KW  - uveal melanoma
KW  - metabolism
KW  - epigenetics
UR  - https://europepmc.org/article/med/32401230
L2  - https://europepmc.org/article/med/32401230
N2  - 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.
ER  -

GIALLONGO, Sebastiano, M. DI ROSA, R. CALTABIANO, L. LONGHITANO, M. REIBALDI, A. DISTEFANO, Oriana LO RE, A. M. AMORINI, L. PUZZO, L. SALVATORELLI, S. PALMUCCI, D. TIBULLO, A. RUSSO, A. LONGO, G. LAZZARINO, G. LI VOLTI a Manlio VINCIGUERRA. Loss of macroH2A1 decreases mitochondrial metabolism and reduces the aggressiveness of uveal melanoma cells. \textit{AGING-US}. ORCHARD PARK: IMPACT JOURNALS LLC, 2020, roč.~12, č.~10, s.~9745-9760. ISSN~1945-4589. Dostupné z: https://dx.doi.org/10.18632/aging.103241.

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