Hiwi Knockdown Inhibits the Growth of Lung Cancer in Nude Mice

Abstract

Hiwi, a human homologue of the Piwi family, plays an important role in stem cell self-renewal and is overexpressed in various human tumors. This study aimed to determine whether an RNA interference-based strategy to suppress Hiwi expression could inhibit tumor growth in a xenograft mouse model. A rare population of SSC lo Alde br cells was isolated and identified as lung cancer stem cells in our previous study. Plasmids containing U6 promoter-driven shRNAs against Hiwi or control plasmids were successfully established. The xenograft tumor model was generated by subcutaneously inoculating with lung cancer stem cell SSC lo Alde br cells. After the tumor size reached about 8 mm in diameter, shRNA plasmids were injected into the mice via the tail vein three times a week for two weeks, then xenograft tumor growth was assessed. In nude mice, intravenously delivery of Hiwi shRNA plasmids significantly inhibited tumor growth compared to treatment with control scrambled shRNA plasmids or the vehicle PBS. No mice died during the experiment and no adverse events were observed in mice administered the plasmids. Moreover, delivery of Hiwi shRNA plasmids resulted in a significant suppressed expression of Hiwi and ALDH-1 in xenograft tumor samples, based on immunohistochemical analysis. Thus, shRNA-mediated Hiwi gene silencing in lung cancer stem cells by an effective in vivo gene delivery strategy appeared to be an effective therapeutic approach for lung cancer, and may provide some useful clues for RNAi gene therapy in solid cancers.

Overexpression of Hiwi Promotes Growth of Human Breast Cancer Cells

“…Further immunohitochemistry analyses confirmed that the hiwi blockage also induced a significant suppression in ALDH-1 positive cells in xenograft tumor samples (Liang et al, 2013). Since ALDH-1 is a confirmative marker of the lung cancer stem cells (Liang et al, 2012), it implied that delivery of shRNA-mediated Hiwi gene silencing resulted in the decreased number of lung cancer stem cells and suppressed tumor growth in nude mice.…”

“…and the suppression of hiwi inhibited the growth of gastric cancer cells and induced cell cycle arrest in G2/M phase (Liu et al, 2006). Whereas, hiwi knockdown inhibits the growth of lung cancer in nude mice (Liang et al, 2013). These results suggest that hiwi may be involved in the tumorigenesis of various cancers and is a potential target for cancer therapy.…”

Manipulations in HIWI level exerts influence on the proliferation of human non-small cell lung cancer cells

“…Yang et al demonstrated that the inhibition of HIWI expression was able to significantly reduce tumor growth in a xenograft mouse model (35). Furthermore, immunohistochemical analyses suggested that downregulation of HIWI was associated with a reduced number of aldehyde dehydrogenase (ALDH)-1 positive cells in xenograft tumor samples (36).…”

Novel mutants of theauberginegene

“…In addition, recent data also suggest a role for Aub in tumorigenesis, [34][35][36][37] stem cell identity renewal 17 and in the nervous system. 38 Characterizing the role and the genetic interactions of aub in the different tissues is essential.…”