RNA-seq and ChIP-seq Identification of Unique and Overlapping Targets of GLI Transcription Factors in Melanoma Cell Lines

Kurtović, Matea; Piteša, Nikolina; Bartoniček, Nenad; Ozretić, Petar; Musani, Vesna; Čonkaš, Josipa; Petrić, Tina; King, Cecile; Sabol, Maja

doi:10.3390/cancers14184540

Pregled bibliografske jedinice broj: 1221249

RNA-seq and ChIP-seq Identification of Unique and Overlapping Targets of GLI Transcription Factors in Melanoma Cell Lines

Kurtović, Matea; Piteša, Nikolina; Bartoniček, Nenad; Ozretić, Petar; Musani, Vesna; Čonkaš, Josipa; Petrić, Tina; King, Cecile; Sabol, Maja

RNA-seq and ChIP-seq Identification of Unique and Overlapping Targets of GLI Transcription Factors in Melanoma Cell Lines // Cancers, 14 (2022), 18; 4540, 20 doi:10.3390/cancers14184540 (međunarodna recenzija, članak, znanstveni)

CROSBI ID: 1221249 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
RNA-seq and ChIP-seq Identification of Unique and Overlapping Targets of GLI Transcription Factors in Melanoma Cell Lines

Autori
Kurtović, Matea ; Piteša, Nikolina ; Bartoniček, Nenad ; Ozretić, Petar ; Musani, Vesna ; Čonkaš, Josipa ; Petrić, Tina ; King, Cecile ; Sabol, Maja

Izvornik
Cancers (2072-6694) 14 (2022), 18; 4540, 20

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

Ključne riječi
melanoma ; HH-GLI pathway ; GLI targets ; MAPK pathway ; targeted therapy

Sažetak
Background: Despite significant progress in therapy, melanoma still has a rising incidence worldwide, and novel treatment strategies are needed. Recently, researchers have recognized the involvement of the Hedgehog-GLI (HH-GLI) signaling pathway in melanoma and its consistent crosstalk with the MAPK pathway. In order to further investigate the link between the two pathways and to find new target genes that could be considered for combination therapy, we set out to find transcriptional targets of all three GLI proteins in melanoma. Methods: We performed RNA sequencing on three melanoma cell lines (CHL-1, A375, and MEL224) with overexpressed GLI1, GLI2, and GLI3 and combined them with the results of ChIP-sequencing on endogenous GLI1, GLI2, and GLI3 proteins. After combining these results, 21 targets were selected for validation by qPCR. Results: RNA-seq revealed a total of 808 differentially expressed genes (DEGs) for GLI1, 941 DEGs for GLI2, and 58 DEGs for GLI3. ChIP-seq identified 527 genes that contained GLI1 binding sites in their promoters, 1103 for GLI2 and 553 for GLI3. A total of 15 of these targets were validated in the tested cell lines, 6 of which were detected by both RNA-seq and ChIP-seq. Conclusions: Our study provides insight into the unique and overlapping transcriptional output of the GLI proteins in melanoma. We suggest that our findings could provide new potential targets to consider while designing melanoma-targeted therapy.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

POVEZANOST RADA

Projekti:
HRZZ-IP-2018-01-4889 - Regulacija GLI koda u tumorima ovisnim o BRAF/NRAS mutacijama (GLIcode) (Sabol, Maja, HRZZ - 2018-01) ( CroRIS)

Ustanove:
Institut "Ruđer Bošković", Zagreb

Profili:

Maja Sabol (autor)