MiR-615-5p depresses natural killer cells cytotoxicity through repressing IGF-1R in hepatocellular carcinoma patients

Abstract

miR-615-5p was characterized by our group as a tumour suppressor. IGF-1 R activates a downstream signalling pathway, well characterized in liver cells, however, its role in immunity especially Natural Killer cells (NKs) remains vague. This study aimed at investigating the regulatory role of miR-615-5p on IGF signalling and its impact on NKs cytotoxicity in HCC. Our results showed an upregulation in miR-615-5p and IGF-1 R in NKs of 130 HCC patients compared to 35 controls. Forcing the expression of miR-615-5p, repressed IGF-IR, attenuated NKs cytotoxicity, decreased CD56^dim, increased CD56^bright NK subsets and reduced the cytotoxic markers NKG2D, TNF-α and perforins. It repressed NKG2D ligand (ULBP2) in Huh-7 cells. In conclusion, miR-615-5p represses IGF-1 R in NKs and their target hepatocytes; however, it has a contradicting impact on HCC progression on both cell types. These findings might pave the way for better understanding the role of microRNAs in NKs function and HCC immune-pathogenesis.

Keywords:

• Hepatocellular carcinoma
• natural killer cells
• insulin-like growth factor axis
• microRNA "miR-615-5p"
• immunotherapy

Acknowledgements

The authors would also like to acknowledge the English department at the German University in Cairo for their support in revising the English in the manuscript.

Disclosure statement

The authors fully declare no financial or potential conflict of interest.