Naslov
Genes for competing endogenous RNAs as targets of transcription factors GLI in melanoma cell lines

Autori
Piteša, Nikolina ; Bartoniček, Nenad ; Kurtović, Matea ; Musani, Vesna ; Trnski, Diana ; Ozretić, Petar ; Sabol, Maja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Serbian Association for Cancer Research-5th Congress of SDIR: Translational Potential of Cancer Research in Serbia (Abstract book) / Đorđić Crnogorac, Marija ; Nedeljković, Milica - Beograd : Srpsko društvo istraživača raka, 2021, 9-9

ISBN
978-86-919183-3-0

Skup
5th Congress of the Serbian Association for Cancer Research (SDIR)

Mjesto i datum
Online, 03.12.2021. - 03.12.2021

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
ChIP-Seq ; lncRNAs ; MAP3 Kinase ; melanoma ; miRNAs

Sažetak
Hedgehog-GLI (HH-GLI) signaling is a conserved signaling pathway reported to be aberrantly activated in various human cancers, including melanoma. Beside its canonical signaling, HH-GLI can also be activated noncanonically through interactions with other signaling pathways like MAPK. Both result in activation of GLI transcription factors. Our previous studies demonstrated that BRAF and NRAS mutated melanoma cell lines have different response following HH- GLI inhibition, which indicates that HH-GLI potentially has a different role in BRAF and NRAS mutated melanoma. To identify GLI transcriptional targets, we performed ChIP-Seq. Firstly, 14 collected melanoma cell lines were sequenced and divided into categories based on their BRAF and NRAS mutation background. Three cell lines with the strongest basal GLI protein expression were selected (A375 BRAFmut, CHL-1 wt and MEL224 NRASmut). Selected target genes were analyzed in silico and validated by qPCR. ChIP-seq analysis revealed 603 potential GLI targets of which 30% have GLI1, 66% GLI2 and 21% GLI3 binding sites. Only 3.8% were mutual for all three GLI proteins. Besides protein coding genes, 20 miRNAs and 29 lncRNAs were identified. miRNA analysis revealed that 50% of identified miRNAs regulate genes related to MAPK signaling. Validation included selected 23 protein coding genes, 9 miRNAs and 3 lncRNAs involved in regulation of MAPK signaling pathway. We validated 4 miRNAs and 2 lncRNAs and constructed a potential GLI-lncRNA-miRNA interactome which will further be examined. Future analysis can potentially bring new insights into miRNA-lncRNA regulatory networks involved in HH- GLI and MAPK interplay.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

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