Interferon regulatory factor 1 (IRF-1) downregulates Checkpoint kinase 1 (CHK1) through miR-195 to upregulate apoptosis and PD-L1 expression in Hepatocellular carcinoma (HCC) cells

Menée à l'aide de données du projet "The Cancer Genome Atlas" et à l'aide d'échantillons tissulaires de carcinomes hépatocellulaires, cette étude met en évidence un mécanisme par lequel le facteur IRF-1, en réduisant l'expression de la kinase CHK1 via le microARN miR-195, augmente l'apoptose des cellules cancéreuses et l'expression de PDL-1 par ces dernières

Résumé en anglais

Background : CHK1 is considered an oncogene with overexpression in numerous cancers. However, CHK1 signalling regulation in hepatocellular carcinoma (HCC) remains unclear.

Methods : CHEK1 mRNA, protein, pri-miR-195 and miR-195 expression in HCC tissue was determined by qPCR, WB and IF staining assay. Survival analyses in HCC with high- and low-CHEK1 mRNA expression was performed using TCGA database. Relative luciferase activity was investigated in HCC cells transfected with p-CHEK1 3’UTR. Apoptosis was detected by TUNEL assay. NK and CD8+ T cells were analysed by flow cytometry.

Results : CHK1 is increased in human HCC tumours compared with non-cancerous liver. High CHK1 predicts worse prognosis. IFN-