Overexpression of Hiwi Promotes Growth of Human Breast Cancer Cells

Abstract

The Piwi subfamily comprises two argonaute (Ago) family proteins, which are defined by the presence of PAZand Piwi domains, with well known roles in RNA silencing. Hiwi, a human Piwi subfamily member, has beenshown to play essential roles in stem cell self-renewal and gametogenesis. Recently, accumulating reports haveindicated that abnormal hiwi expression is associated with poorer prognosis of multiple types of human cancers,including examples in the breast. However, little is known about details of the oncogenic role of hiwi in breastcancers. In present study, we confirmed overexpression of hiwi in breast cancer specimens and breast cancercell lines at both mRNA and protein levels. Thus both RT-qPCR and Western blot data revealed significantlyhigher hiwi in intratumor than peritumor specimens, overexpression being associated with tumor size, lymphnode metastasis and histological grade. Hiwi overexpression was also identified in breast cancer cell lines, MDAMB-231 and MCF-7, and gain-of-function and loss-of-function strategies were adopted to identify the role ofhiwi in the MCF-7 cell growth. Results demonstrated that hiwi expression in MCF-7 cells was significantly up- ordown- regulated by the two strategies. We next evaluated the influence of hiwi overexpression or knockdownon the growth of breast cancer cells. Both cell count and colony formation assays confirmed promoting rolesof hiwi in MCF-7 cells, which could be inhibited by hiwi specific blockage by siRNAs. In summary, the presentstudy confirmed overexpression of hiwi in breast cancer specimens and breast cancer cell lines, and providede vidence of promotion by hiwi of cell growth. The results imply an oncogenic role of hiwi in breast cancers.