DOI QR코드

DOI QR Code

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)
  • 발행 : 2014.10.11

초록

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.

참고문헌

  1. Brackstone M, Townson JL, Chambers AF (2007). Tumour dormancy in breast cancer: an update. Breast Cancer Res, 9, 208. https://doi.org/10.1186/bcr1677
  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. https://doi.org/10.1093/nar/gkf579
  4. 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. https://doi.org/10.1016/S0968-0004(00)01641-8
  5. 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. https://doi.org/10.1038/35078107
  6. Eng C, Stratton M, Ponder B, et al (1994). Familial cancer syndromes. Lancet, 343, 709-13. https://doi.org/10.1016/S0140-6736(94)91585-7
  7. 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. https://doi.org/10.7314/APJCP.2014.15.8.3805
  8. 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. https://doi.org/10.1038/sj.bjc.6604653
  9. Hall TM (2005). Structure and function of argonaute proteins. Structure, 13, 1403-8. https://doi.org/10.1016/j.str.2005.08.005
  10. 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. https://doi.org/10.1186/1471-2407-9-426
  11. Hochedlinger K, Jaenisch R (2006). Nuclear reprogramming and pluripotency. Nature, 441, 1061-7. https://doi.org/10.1038/nature04955
  12. 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. https://doi.org/10.1016/j.cell.2007.03.026
  13. Husemann Y, Geigl JB, Schubert F, et al (2008). Systemic spread is an early step in breast cancer. Cancer Cell, 13, 58-68. https://doi.org/10.1016/j.ccr.2007.12.003
  14. 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. https://doi.org/10.7314/APJCP.2013.14.2.1067
  15. Hutvagner G, Simard MJ (2008). Argonaute proteins: key players in RNA silencing. Nat Rev Mol Cell Biol, 9, 22-32. https://doi.org/10.1038/nrm2321
  16. Klein CA (2009). Parallel progression of primary tumours and metastases. Nat Rev Cancer, 9, 302-12. https://doi.org/10.1038/nrc2627
  17. 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. https://doi.org/10.1371/journal.pone.0059203
  18. Liang D, Shi Y (2012). Aldehyde dehydrogenase-1 is a specific marker for stem cells in human lung adenocarcinoma. Med Oncol, 29, 633-9. https://doi.org/10.1007/s12032-011-9933-9
  19. Lingel A, Sattler M (2005). Novel modes of protein-RNA recognition in the RNAi pathway. Curr Opin Struct Biol, 15, 107-15. https://doi.org/10.1016/j.sbi.2005.01.010
  20. 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. https://doi.org/10.1002/ijc.21575
  21. 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. https://doi.org/10.1006/meth.2001.1262
  22. 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. https://doi.org/10.7314/APJCP.2014.15.4.1783
  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. https://doi.org/10.1002/pbc.24223
  24. Ocana A, Pandiella A (2008). Identifying breast cancer druggable oncogenic alterations: lessons learned and future targeted options. Clin Cancer Res, 14, 961-70. https://doi.org/10.1158/1078-0432.CCR-07-1630
  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. https://doi.org/10.1002/(SICI)1097-0142(19960215)77:4<697::AID-CNCR16>3.0.CO;2-W
  26. 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. https://doi.org/10.7314/APJCP.2014.15.7.3041
  27. Meister G, Tuschl T (2004). Mechanisms of gene silencing by double-stranded RNA. Nature, 431, 343-9. https://doi.org/10.1038/nature02873
  28. Oh SJ, Kim SM, Kim YO, Chang HK (2012). Clinicopathologic Implications of PIWIL2 expression in colorectal cancer. Korean J Pathol, 46, 318-23. https://doi.org/10.4132/KoreanJPathol.2012.46.4.318
  29. 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. https://doi.org/10.1038/sj.emboj.7600488
  30. Peters L, Meister G (2007). Argonaute proteins: mediators of RNA silencing. Mol Cell, 26, 611-23. https://doi.org/10.1016/j.molcel.2007.05.001
  31. 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. https://doi.org/10.1093/carcin/bgt404
  32. 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. https://doi.org/10.1038/sj.onc.1205505
  33. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001). Stem cells, cancer, and cancer stem cells. Nature, 414, 105-11. https://doi.org/10.1038/35102167
  34. Sana J, Faltejskova P, Svoboda M, Slaby O (2012). Novel classes of non-coding RNAs and cancer. J Transl Med, 10, 103. https://doi.org/10.1186/1479-5876-10-103
  35. 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. https://doi.org/10.1136/jcp.2003.010777
  36. 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. https://doi.org/10.1182/blood.V97.2.426
  37. 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. https://doi.org/10.1038/nbt957
  38. Szymczak-Workman AL, Vignali KM, Vignali DA (2012). Verification of 2A peptide cleavage. Cold Spring Harb Protoc, 2012, 255-7.
  39. 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. https://doi.org/10.1186/bcr3102
  40. Yan KS, Yan S, Farooq A, et al (2003). Structure and conserved RNA binding of the PAZ domain. Nature, 426, 468-74. https://doi.org/10.1038/nature02129
  41. 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. https://doi.org/10.1002/cncr.26524

피인용 문헌

  1. PIWIL2 promotes progression of non-small cell lung cancer by inducing CDK2 and Cyclin A expression vol.13, pp.1, 2015, https://doi.org/10.1186/s12967-015-0666-y
  2. Emerging roles for PIWI proteins in cancer vol.47, pp.5, 2015, https://doi.org/10.1093/abbs/gmv018
  3. Overexpression of Hiwi Inhibits the Growth and Migration of Chronic Myeloid Leukemia Cells vol.73, pp.1, 2015, https://doi.org/10.1007/s12013-015-0651-3
  4. Overexpression of Hiwi Inhibits the Cell Growth of Chronic Myeloid Leukemia K562 Cells and Enhances Their Chemosensitivity to Daunomycin vol.73, pp.1, 2015, https://doi.org/10.1007/s12013-015-0668-7
  5. Predicting the Correlation of EZH2 and Cancer Stem Cell Markers in Esophageal Squamous Cell Carcinoma pp.1941-6636, 2017, https://doi.org/10.1007/s12029-017-9985-y
  6. The meaning of PIWI proteins in cancer development vol.13, pp.5, 2017, https://doi.org/10.3892/ol.2017.5932
  7. Piwi-like 1 and -2 protein expression levels are prognostic factors for muscle invasive urothelial bladder cancer patients vol.8, pp.1, 2018, https://doi.org/10.1038/s41598-018-35637-4
  8. MicroRNA Biogenesis Pathway Gene Polymorphisms Are Associated with Breast Cancer Risk vol.54, pp.5, 2018, https://doi.org/10.1134/S1022795418040051