Abstract

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. MicroRNA (miRNA) is endogenous noncoding RNA that processes a variety of physiological functions, including tumorigenesis and cancer development. Therefore, restoring the aberrant expression of oncogenic miRNA in HCC offers a promising therapeutic strategy. MiRNA-21 (miR-21) is reportedly associated with tumor proliferation by suppressing numerous tumor suppressor genes. Therefore, the aim of this study was to investigate whether miR-21 inhibition can suppress tumor growth in HCC. We measured the expression of miR21 in clinical samples from HCC patients and HCC cell lines subjected to hypoxia. The expected target genes of miR-21 were analyzed using computational methods and the luciferase assay was performed to confirm that they were suppressed by miR-21. Furthermore, the tumor suppression effect of miR-21 inhibitor combined with sorafenib was investigated using the orthotopic HCC mouse model. The tissues from HCC patients showed elevated expression of miR-21. In addition, the HCC cell line showed increased expression of miR-21 when exposed to hypoxic conditions. Among expected miR-21 target genes, SASH1 was significantly suppressed. HCC cells treated with miR-21 inhibitor showed decreased proliferation and increased apoptotic death whereas miR-21 mimics increased cell population. In orthotopic HCC models, miR-21 inhibitor combined with sorafenib suppressed tumor growth while restoring SASH1 expression. The current study suggests that miR-21 plays an important role in promoting HCC tumorigenesis via suppressing SASH1. Accordingly, the combined treatment of sorafenib with miR-21 inhibitor offers a promising strategy for HCC.