Contradicting interplay between insulin-like growth factor-1 and miR-486-5p in primary NK cells and hepatoma cell lines with a contemporary inhibitory impact on HCC tumor progression

Abstract

In this study, an impaired natural killer (NK) cell cytolytic activity in 135 hepatocellular carcinoma (HCC) patients parallel to a reduced expression level of insulin-like growth factor (IGF)-1 in NK cells of HCC patients has been revealed. Ectopic expression of miR-486-5p, a direct upstream regulator of IGF-1, restored the endogenous level of IGF-1 in NK cells of HCC patients, thus augmenting its cytolytic activity against Huh7 cells in an opposite manner to the IGF-1 siRNAs. Unorthodoxly, over-expression of miR-486-5p in target hepatocytes resulted in the repression of IGF-1, suppression of Huh7 cells proliferation and viability in a similar pattern to the IGF-1 siRNAs. Therefore, this study highlights a potential role of IGF-1 in modulating cytolytic potential of NK cells of HCC patients. miR-486-5p acts in a cell-specific manner, differentially modulating IGF-1 expression in NK cells and their target hepatocytes with a contemporary inhibitory impact on HCC progression.

• Insulin-like growth factor-1
• natural killer cells
• miR-486-5p
• hepatocellular carcinoma
• immunotherapy
• perforins
• NKG2D
• NKG2A

Acknowledgements

The authors acknowledge the English instructor, Ms. Mai Magdy Selim, and the English Department at the German University in Cairo for revising the manuscript. The authors would also like to acknowledge all the Molecular Pathology Research Group members for their valuable support and guidance in this study.

Declaration of interest

The authors have declared that no competing interests exist.