Browse > Article
http://dx.doi.org/10.7314/APJCP.2014.15.18.7553

Overexpression of Hiwi Promotes Growth of Human Breast Cancer Cells  

Wang, Da-Wei (Central Research Department, China-Japan Union Hospital of Jilin University)
Wang, Zhao-Hui (Department of Neurology, the Affiliated Hospital of Beihua University)
Wang, Ling-Ling (Department of Neurology, the Affiliated Hospital of Beihua University)
Song, Yang (Central Research Department, China-Japan Union Hospital of Jilin University)
Zhang, Gui-Zhen (Central Research Department, China-Japan Union Hospital of Jilin University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.18, 2014 , pp. 7553-7558 More about this Journal
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 e vidence of promotion by hiwi of cell growth. The results imply an oncogenic role of hiwi in breast cancers.
Keywords
Hiwi; growth; human breast cancer cells;
Citations & Related Records
Times Cited By KSCI : 5  (Citation Analysis)
연도 인용수 순위
1 Brackstone M, Townson JL, Chambers AF (2007). Tumour dormancy in breast cancer: an update. Breast Cancer Res, 9, 208.   DOI
2 Brown S (2011). Row brewing over the relevance of survival or mortality rates in breast cancer. Menopause Int, 17, 75-6.
3 Fetzer CP, Hogan DJ, Lipps HJ (2002). A PIWI homolog is one of the proteins expressed exclusively during macronuclear development in the ciliate Stylonychia lemnae. Nucleic Acids Res, 30, 4380-6.   DOI   ScienceOn
4 Elbashir SM, Harborth J, Lendeckel W, et al (2001). Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature, 411, 494-8.   DOI   ScienceOn
5 Eng C, Stratton M, Ponder B, et al (1994). Familial cancer syndromes. Lancet, 343, 709-13.   DOI   ScienceOn
6 Floriano-Sanchez E, Rodriguez NC, Bandala C, et al (2014). CYP3A4 expression in breast cancer and its association with risk factors in Mexican women. Asian Pac J Cancer Prev, 15, 3805-9.   과학기술학회마을   DOI   ScienceOn
7 Grochola LF, Greither T, Taubert H, et al (2008). The stem cell-associated Hiwi gene in human adenocarcinoma of the pancreas: expression and risk of tumour-related death. Br J Cancer, 99, 1083-8.   DOI   ScienceOn
8 Hall TM (2005). Structure and function of argonaute proteins. Structure, 13, 1403-8.   DOI   ScienceOn
9 He W, Wang Z, Wang Q, et al (2009). Expression of HIWI in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis. BMC Cancer, 9, 426.   DOI   ScienceOn
10 Hochedlinger K, Jaenisch R (2006). Nuclear reprogramming and pluripotency. Nature, 441, 1061-7.   DOI   ScienceOn
11 Houwing S, Kamminga LM, Berezikov E, et al (2007). A role for Piwi and piRNAs in germ cell maintenance and transposon silencing in Zebrafish. Cell, 129, 69-82.   DOI   ScienceOn
12 Husemann Y, Geigl JB, Schubert F, et al (2008). Systemic spread is an early step in breast cancer. Cancer Cell, 13, 58-68.   DOI   ScienceOn
13 Liang D, Dong M, Hu LJ, et al (2013). Hiwi knockdown inhibits the growth of lung cancer in nude mice. Asian Pac J Cancer Prev, 14, 1067-72.   과학기술학회마을   DOI   ScienceOn
14 Hutvagner G, Simard MJ (2008). Argonaute proteins: key players in RNA silencing. Nat Rev Mol Cell Biol, 9, 22-32.   DOI   ScienceOn
15 Klein CA (2009). Parallel progression of primary tumours and metastases. Nat Rev Cancer, 9, 302-12.   DOI   ScienceOn
16 Li Z, Tian T, Lv F, et al (2013). Six1 promotes proliferation of pancreatic cancer cells via upregulation of cyclin D1 expression. PLoS One, 8, e59203.   DOI
17 Liang D, Shi Y (2012). Aldehyde dehydrogenase-1 is a specific marker for stem cells in human lung adenocarcinoma. Med Oncol, 29, 633-9.   DOI   ScienceOn
18 Lingel A, Sattler M (2005). Novel modes of protein-RNA recognition in the RNAi pathway. Curr Opin Struct Biol, 15, 107-15.   DOI   ScienceOn
19 Liu X, Sun Y, Guo J, et al (2006). Expression of hiwi gene in human gastric cancer was associated with proliferation of cancer cells. Int J Cancer, 118, 1922-9.   DOI   ScienceOn
20 Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 25, 402-8.   DOI   ScienceOn
21 Madjd Z, Akbari ME, Zarnani AH, et al (2014). Expression of EMSY, a novel BRCA2-link protein, is associated with lymph node metastasis and increased tumor size in breast carcinomas. Asian Pac J Cancer Prev, 15, 1783-9.   과학기술학회마을   DOI   ScienceOn
22 Medina-Jaime AD, Reyes-Vargas F, Martinez-Gaytan V, et al (2014). Esr1 and pgr gene promoter methylation and correlations with estrogen and progesterone receptors in ductal and lobular breast cancer. Asian Pac J Cancer Prev, 15, 3041-4.   과학기술학회마을   DOI   ScienceOn
23 Magnusson S, Gisselsson D, Wiebe T, et al (2012). Prevalence of germline TP53 mutations and history of Li-Fraumeni syndrome in families with childhood adrenocortical tumors, choroid plexus tumors, and rhabdomyosarcoma: a population-based survey. Pediatr Blood Cancer, 59, 846-53.   DOI   ScienceOn
24 Ocana A, Pandiella A (2008). Identifying breast cancer druggable oncogenic alterations: lessons learned and future targeted options. Clin Cancer Res, 14, 961-70.   DOI   ScienceOn
25 Marcus JN, Watson P, Page DL, et al (1996). Hereditary breast cancer: pathobiology, prognosis, and BRCA1 and BRCA2 gene linkage. Cancer, 77, 697-709.   DOI
26 Meister G, Tuschl T (2004). Mechanisms of gene silencing by double-stranded RNA. Nature, 431, 343-9.   DOI   ScienceOn
27 Oh SJ, Kim SM, Kim YO, Chang HK (2012). Clinicopathologic Implications of PIWIL2 expression in colorectal cancer. Korean J Pathol, 46, 318-23.   DOI   ScienceOn
28 Parker JS, Roe SM, Barford D (2004). Crystal structure of a PIWI protein suggests mechanisms for siRNA recognition and slicer activity. EMBO J, 23, 4727-37.   DOI   ScienceOn
29 Peters L, Meister G (2007). Argonaute proteins: mediators of RNA silencing. Mol Cell, 26, 611-23.   DOI   ScienceOn
30 Purrington KS, Slager S, Eccles D, et al (2014). Genomewide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer. Carcinogenesis, 35, 1012-9.   DOI   ScienceOn
31 Qiao D, Zeeman AM, Deng W, et al (2002). Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas. Oncogene, 21, 3988-99.   DOI   ScienceOn
32 Reya T, Morrison SJ, Clarke MF, Weissman IL (2001). Stem cells, cancer, and cancer stem cells. Nature, 414, 105-11.   DOI   ScienceOn
33 Sana J, Faltejskova P, Svoboda M, Slaby O (2012). Novel classes of non-coding RNAs and cancer. J Transl Med, 10, 103.   DOI
34 Sharma AK, Nelson MC, Brandt JE, et al (2001). Human CD34(+) stem cells express the hiwi gene, a human homologue of the Drosophila gene piwi. Blood, 97, 426-34.   DOI   ScienceOn
35 Szymczak AL, Workman CJ, Wang Y, et al (2004). Correction of multi-gene deficiency in vivo using a single 'self-cleaving' 2A peptide-based retroviral vector. Nat Biotechnol, 22, 589-94.   DOI   ScienceOn
36 Szymczak-Workman AL, Vignali KM, Vignali DA (2012). Verification of 2A peptide cleavage. Cold Spring Harb Protoc, 2012, 255-7.
37 Yan KS, Yan S, Farooq A, et al (2003). Structure and conserved RNA binding of the PAZ domain. Nature, 426, 468-74.   DOI   ScienceOn
38 Zhao YM, Zhou JM, Wang LR, et al (2012). HIWI is associated with prognosis in patients with hepatocellular carcinoma after curative resection. Cancer, 118, 2708-17.   DOI   ScienceOn
39 van Diest PJ, van der Wall E, Baak JP (2004). Prognostic value of proliferation in invasive breast cancer: a review. J Clin Pathol, 57, 675-81.   DOI   ScienceOn
40 Cerutti L, Mian N, Bateman A (2000). Domains in gene silencing and cell differentiation proteins: the novel PAZ domain and redefinition of the Piwi domain. Trends Biochem Sci, 25, 481-2.   DOI   ScienceOn
41 Weng D, Penzner JH, Song B, et al (2012). Metastasis is an early event in mouse mammary carcinomas and is associated with cells bearing stem cell markers. Breast Cancer Res, 14, 18.   DOI   ScienceOn