Naslov
ASSOCIATION OF PERIOD CIRCADIAN GENES WITH CHEMORESISTANCE OF COLON CANCER CELLS WITH BRAFV600E MUTATION

Autori
Markova-Car, Elitza ; Ripić, Martin ; Sedić, Mirela

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

Izvornik
Pharmaca / - , 2022, 142-142

Skup
10. hrvatski kongres farmakologije ; 1. hrvatski kongres kliničke farmakologije s međunarodnim sudjelovanjem = 10th Croatian Congress of Pharmacology ; 1st Croatian Congress of Clinical Pharmacology and Therapeutics with International Participation

Mjesto i datum
Opatija, Hrvatska, 22.09.2022. - 25.09.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
circadian rhythm, clock genes, PER genes, colorectal cancer with BRAFV600E mutation, chemoresistance

Sažetak
Introduction: Colorectal cancer is one of the most common cancers worldwide with approximately 5-10% of all cases carrying BRAFV600E mutation. Despite increasingly improved chemotherapy options, no significant advancement was observed in the treatment outcome of BRAF mutated patients, mainly due to the development of chemoresistance. The circadian system is involved in a number of cellular processes such as the cell cycle, DNA repair, metabolism and regulation of apoptosis. Consequently, in recent years there has been a growing interest in exploring possible links between the circadian system and tumorigenesis. Here, we investigated the relationship between circadian clock genes and acquired resistance to vemurafenib in colon cancer cells with the BRAFV600E mutation. Materials and methods: The expression profiles of circadian clock genes in chemosensitive versus chemoresistant RKO colon cancer cells with BRAFV600E mutation were analyzed using the qPCR method. In silico analysis of selected genes was performed using the TCGA Colorectal Adenocarcinoma (TCGA, PanCancer Atlas) dataset. Results: The expression of PER genes was significantly higher in chemoresistant cells. Among these, PER3 gene showed the highest expression level in chemoresistant cells. Importantly, mRNA levels of PER3 were also significantly increased in BRAFV600E mutated colon cancer patients in comparison with an unaltered group in the TCGA colorectal cancer dataset. Higher mRNA level of PER3 was also associated with shorter overall survival of BRAF mutated colon cancer patients. Conclusions: Our results suggested a possible role for PER3 in acquired resistance to vemurafenib and survival outcomes in BRAFV600E-mutated colon cancer.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA