Hiwi downregulation, mediated by shRNA, reduces the proliferation and migration of human hepatocellular carcinoma cells

Abstract

The Piwi subfamily is one of two Argonaute family proteins, which are characterized by the presence of Piwi and PiwiArgonauteZwille domains, and are well known for their role in RNA silencing. Hiwi, a human member of the Piwi subfamily, is restricted to the germ line, where it binds Piwiinteracting RNAs and functions in stem cell selfrenewal and gametogenesis. Previous reports have indicated that abnormal Hiwi expression may be associated with a poor prognosis of numerous types of human cancer, including hepatocellular carcinoma (HCC). However, little is currently known about the oncogenic role of Hiwi in HCC. In the present study, it was confirmed that Hiwi is overexpressed at both the mRNA and protein level, in HCC specimens, as well as in MHCC97L and MHCC97H HCC cell lines. A lentivirusmediated small hairpin RNA (shRNA) targeting Hiwi was constructed and used to infect MHCC97L and MHCC97H cells. Relative Hiwi mRNA and protein expression levels were determined by quantitative polymerase chain reaction and western blot analysis, respectively. Cell proliferation, migration and invasion were determined using cell count, scratch and Transwell assays, respectively. Hiwi mRNA and protein expression was significantly downregulated in HCC cells in response to transduction with the lentivirusmediated shRNA. Furthermore, the proliferative, migrative and invasive properties of the shRNAtransduced cells were significantly decreased. Therefore, Hiwi downregulation mediated by shRNA, may reduce the proliferation and migration of HCC cells. These results indicate that Hiwi may have an important role in the progression of HCC and may be a target for anticancer therapy.