Abstract

BackgroundRecent studies have suggested that B7-H6, a new member of the B7 family of ligands, not only is a crucial regulator of NK cell-mediated immune responses but also has important clinical implications due to its abnormal expression in many human cancers. We have previously reported that higher B7-H6 expression levels in ovarian cancer tissues are positively correlated with tumor metastasis and cancer progression. To date, the expression of B7-H6 in human hepatocellular carcinoma (HCC) and the clinical significance of B7-H6 expression still remain elusive.MethodsIn the present study, the expression level of B7-H6 was examined in both HCC tissues and HCC cell lines (HepG2 and SMMC-7721). And the clinical significance of B7-H6 was analyzed as well.ResultsOur results revealed that B7-H6 was expressed abnormally in HCC tissues, which was greatly related to tumor size. The TCGA data also showed that the B7-H6 mRNA expression level was significantly negatively correlated with the survival of HCC patients. Next, to investigate the functions of B7-H6 in HCC, we successfully constructed B7-H6 knockdown expression human HCC cell lines using the RNA interference technology. Our studies showed that reduced expression of B7-H6 in HepG2 and SMMC-7721 cells significantly attenuated cell proliferation as well as cell migration and invasion. Besides, depletion of B7-H6 greatly induced cell cycle arrest at G1 phase. And also B7-H6 knockdown in HCC cell lines dramatically decreased the C-myc, C-fos and Cyclin-D1 expression.ConclusionsOur present findings suggested that B7-H6 played an important role in oncogenesis of HCC on cellular level, and B7-H6 could be employed to develop immunotherapeutic approaches targeting this malignancy.

Highlights

  • Recent studies have suggested that B7-H6, a new member of the B7 family of ligands, is a crucial regulator of natural killer (NK) cell-mediated immune responses and has important clinical implications due to its abnormal expression in many human cancers

  • We aimed to identify the clinical significance of B7-H6 expression in human hepatocellular carcinoma (HCC) tissues and to further investigate the role of B7-H6 expression in regulating cellular functions in HCC cell lines

  • Our data demonstrated that B7-H6 expression in the human HCC tissues was significantly associated with the age (P = 0.015) and tumor size (P = 0.034) of the patients

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Summary

Introduction

Recent studies have suggested that B7-H6, a new member of the B7 family of ligands, is a crucial regulator of NK cell-mediated immune responses and has important clinical implications due to its abnormal expression in many human cancers. The expression of B7-H6 in human hepatocellular carcinoma (HCC) and the clinical significance of B7-H6 expression still remain elusive. To date, the exact role of B7-H6 expression in the oncogenesis and progression of HCC remains largely unexplored. We aimed to identify the clinical significance of B7-H6 expression in human HCC tissues and to further investigate the role of B7-H6 expression in regulating cellular functions in HCC cell lines

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