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Knock-down of AHCY and depletion of adenosine induces DNA damage and cell cycle arrest


Belužić, Lucija; Grbeša, Ivana; Belužić, Robert; Park, Jong Hoon; Kong, Hyun Kyung; Kopjar, Nevenka; Espadas, Guadalupe; Sabidó, Eduard; Lepur, Adriana; Rokić, Filip et al.
Knock-down of AHCY and depletion of adenosine induces DNA damage and cell cycle arrest // Scientific Reports, 8 (2018), 14012, 16 doi:10.1038/s41598-018-32356-8 (međunarodna recenzija, članak, znanstveni)


Naslov
Knock-down of AHCY and depletion of adenosine induces DNA damage and cell cycle arrest

Autori
Belužić, Lucija ; Grbeša, Ivana ; Belužić, Robert ; Park, Jong Hoon ; Kong, Hyun Kyung ; Kopjar, Nevenka ; Espadas, Guadalupe ; Sabidó, Eduard ; Lepur, Adriana ; Rokić, Filip ; Jerić, Ivanka ; Brkljačić, Lidija ; Vugrek, Oliver

Izvornik
Scientific Reports (2045-2322) 8 (2018); 14012, 16

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
DNA damage ; liver cancer ; RNAseq ; SILAC ; methylation potential, SAM/SAH ratio
(DNA damage ; liver cancer ; RNAseq ; SILAC ; methylation potential ; SAM/SAH ratio)

Sažetak
Recently, functional connections between S-adenosylhomocysteine hydrolase (AHCY) activity and cancer have been reported. As the properties of AHCY include the hydrolysis of S- adenosylhomocysteine and maintenance of the cellular methylation potential, the connection between AHCY and cancer is not obvious. The mechanisms by which AHCY influences the cell cycle or cell proliferation have not yet been confirmed. To elucidate AHCY- driven cancer-specific mechanisms, we pursued a multi-omics approach to investigate the effect of AHCY-knockdown on hepatocellular carcinoma cells. Here, we show that reduced AHCY activity causes adenosine depletion with activation of the DNA damage response (DDR), leading to cell cycle arrest, a decreased proliferation rate and DNA damage. The underlying mechanism behind these effects might be applicable to cancer types that have either significant levels of endogenous AHCY and/or are dependent on high concentrations of adenosine in their microenvironments. Thus, adenosine monitoring might be used as a preventive measure in liver disease, whereas induced adenosine depletion might be the desired approach for provoking the DDR in diagnosed cancer, thus opening new avenues for targeted therapy. Additionally, including AHCY in mutational screens as a potential risk factor may be a beneficial preventive measure.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Interdisciplinarne prirodne znanosti, Temeljne medicinske znanosti

Napomena
FP7-REGPOT-2012-2013-1, grant agreement number 316289-InnoMol



POVEZANOST RADA


Projekt / tema
EK-FP7-316289 (EK - FP7-REGPOT-2012-2013-1)

Ustanove
Institut "Ruđer Bošković", Zagreb

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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