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.

Basic information

Original name

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

Authors

GIALLONGO, Sebastiano (380 Italy, belonging to the institution), M. DI ROSA (380 Italy), R. CALTABIANO (380 Italy), L. LONGHITANO (380 Italy), M. REIBALDI (380 Italy), A. DISTEFANO (380 Italy), Oriana LO RE (380 Italy, belonging to the institution), A. M. AMORINI (380 Italy), L. PUZZO (380 Italy), L. SALVATORELLI (380 Italy), S. PALMUCCI (380 Italy), D. TIBULLO (380 Italy), A. RUSSO (380 Italy), A. LONGO (380 Italy), G. LAZZARINO (380 Italy), G. LI VOLTI (380 Italy) and Manlio VINCIGUERRA (380 Italy, guarantor)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.682

RIV identification code

RIV/00216224:14110/20:00116011

Organization unit

Faculty of Medicine

DOI

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

UT WoS

000537718700058

Keywords in English

macroH2A1; histones; uveal melanoma; metabolism; epigenetics

Abstract

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 and Manlio VINCIGUERRA. Loss of macroH2A1 decreases mitochondrial metabolism and reduces the aggressiveness of uveal melanoma cells. AGING-US. ORCHARD PARK: IMPACT JOURNALS LLC, 2020, vol. 12, No 10, p. 9745-9760. ISSN 1945-4589. Available from: 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 and 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, vol.~12, No~10, p.~9745-9760. ISSN~1945-4589. Available from: https://dx.doi.org/10.18632/aging.103241.

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