Abstract
The Piwi subfamily comprises two argonaute (Ago) family proteins, which are defined by the presence of PAZ and Piwi domains, with well known roles in RNA silencing. Hiwi, a human Piwi subfamily member, has been shown to play essential roles in stem cell self-renewal and gametogenesis. Recently, accumulating reports have indicated 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 breast cancers. In present study, we confirmed overexpression of hiwi in breast cancer specimens and breast cancer cell lines at both mRNA and protein levels. Thus both RT-qPCR and Western blot data revealed significantly higher hiwi in intratumor than peritumor specimens, overexpression being associated with tumor size, lymph node metastasis and histological grade. Hiwi overexpression was also identified in breast cancer cell lines, MDA- MB-231 and MCF-7, and gain-of-function and loss-of-function strategies were adopted to identify the role of hiwi in the MCF-7 cell growth. Results demonstrated that hiwi expression in MCF-7 cells was significantly up- or down- regulated by the two strategies. We next evaluated the influence of hiwi overexpression or knockdown on the growth of breast cancer cells. Both cell count and colony formation assays confirmed promoting roles of hiwi in MCF-7 cells, which could be inhibited by hiwi specific blockage by siRNAs. In summary, the present study confirmed overexpression of hiwi in breast cancer specimens and breast cancer cell lines, and provided evidence of promotion by hiwi of cell growth. The results imply an oncogenic role of hiwi in breast cancers.
Highlights
Breast cancer leads the cause of death among solid tumours in women, with an increasing incidence, especially among younger woman
Hiwi overexpression was 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 of hiwi in the MCF-7 cell growth
We evaluated the influence of hiwi overexpression or knockdown on the growth of breast cancer cells
Summary
Breast cancer leads the cause of death among solid tumours in women, with an increasing incidence, especially among younger woman (van Diest et al, 2004). There are at present no realistic options for primary prevention in patients, except hereditary breast cancer related genes, such as BRCA1 and BRCA2 (Marcus et al, 1996), PTEN (Cowden’s disease) (Eng et al, 1994), and p53 (Li Fraumeni syndrome) (Magnusson et al, 2012). Multiple molecules have been recognized as pro-oncogenic factors for breast cancers by the universal screen methods basing genomics, transcriptomics, proteotics (Ocana et al, 2008), or other methods. CYP3A4 expression has been recognized as a risk facror of breast cancer in Mexican women
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