Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Lentivirus Mediated GOLPH3 shRNA Inhibits Growth and Metastasis of Esophageal Squamous Cancer

  • Wang, Qiang (First Affiliated Hospital, Henan University of Science and Technology) ;
  • Wang, Xian (First Affiliated Hospital, Henan University of Science and Technology) ;
  • Zhang, Can-Bin (First Affiliated Hospital, Henan University of Science and Technology)
  • Published : 2013.09.30
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Abstract

Aim: To investigate the role of Golgi phosphoprotein 3 (GOLPH3) in tumour growth and metastasis of esophageal squamous cancer. Methods: A lentiviral shRNA-vector was utilized to stably knockdown GOLPH3 in Eca-109 esophageal squamous cancer cells. mRNA transcription and protein expression of GOLPH3 were examined by real-time quantitative PCR and Western blotting, respectively. Cell proliferation activity was assessed by MTT assay and invasion and migration potentials by matrigel invasion and transwell motility assays. Results: Stable knockdown in the GOLPH3 cell line was established. PD-A gene expression was significantly suppressed by lentivirus-mediated RNAi, which resulted in reducing the capacity for cell proliferation, migration, invasion and adhesion in vitro. In vivo, GOLPH3 depletion resulted in inhibition of tumour growth, with stable decrease in the expression of GOLPH3 in tumor xenografts. Conclusions: Our findings suggest that lentivirus mediated silencing of the GOLPH3 gene has a significant anti-tumour effect on esophageal squamous cancer in vitro and in vivo. In addition, the results indicate that GOLPH3 might be an effective molecular target for gene therapy in esophageal squamous cancer.

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References

  1. Boudreau RL, Davidson BL (2012). Generation of hairpin-based RNAi vectors for biological and therapeutic application. Methods Enzymol, 507, 275-96. https://doi.org/10.1016/B978-0-12-386509-0.00014-4
  2. Dippold HC, Ng MM, Farber-Katz SE, et al (2009). GOLPH3 bridges phosphatidylinositol-4- phosphate and actomyosin to stretch and shape the Golgi to promote budding. Cell, 139, 337-51. https://doi.org/10.1016/j.cell.2009.07.052
  3. Dropulic B (2011). Lentiviral vectors: their molecular design, safety, and use in laboratory and preclinical research. Hum Gene Ther, 22, 649-57. https://doi.org/10.1089/hum.2011.058
  4. Feng RH, Zhu ZG, Li JF, et al (2002). Inhibition of human telomerase in MKN- 45 cell line by antisense hTR expression vector induces cell apoptosis and growth arrest. World J Gastroenterol, 8, 436-40. https://doi.org/10.3748/wjg.v8.i3.436
  5. Graham TR, Burd CG (2011). Coordination of Golgi functions by phosphatidylinositol 4-kinases. Trends Cell Biol, 21, 113-21. https://doi.org/10.1016/j.tcb.2010.10.002
  6. Higuchi K, Koizumi W, Tanabe S, et al (2009).Current management of esophageal squamous-cell carcinoma in Japan and other countries. Gastrointest Cancer Res, 3, 153-61.
  7. Hu BS, Hu H, Zhu CY, Gu YL, Li JP (2013). Overexpression of GOLPH3 is associated with poor clinical outcome in gastric cancer. Tumour Biol, 34, 515-20. https://doi.org/10.1007/s13277-012-0576-z
  8. Jiang R, Xue S, Jin Z (2011). Stable knockdown of MYCN by lentivirus-based RNAi inhibits human neuroblastoma cells growth in vitro and in vivo. Biochem Biophys Res Commun, 410, 364-70. https://doi.org/10.1016/j.bbrc.2011.06.020
  9. Jiang Y, Huang C, Lei J, et al (2010).Effects of a regional Chinese diet on proliferation of human esophageal cancer cell line Eca-109 by a sero-physiology method. Nutr Cancer, 62, 543-53. https://doi.org/10.1080/01635580903532465
  10. Kelly P, Moeller BJ, Juneja J, et al (2006a). The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis. Proc Natl Acad Sci USA, 103, 8173 -81. https://doi.org/10.1073/pnas.0510254103
  11. Kelly P, Stemmle LN, Madden JF, et al (2006b). A role for the G12 family of heterotrimeric G-proteins in prostate cancer invasion. J Biol Chem, 281, 26483-90. https://doi.org/10.1074/jbc.M604376200
  12. Kunigou O, Nagao H, Kawabata N, et al (2011). Role of GOLPH3 and GOLPH3L in the proliferation of human rhabdomyosarcoma. Oncol Rep, 26, 1337-42.
  13. Li XY, Liu W, Chen SF, et al (2011). Expression of the Golgi phosphoprotein-3 gene in human gliomas: a pilot study. J Neurooncol, 105, 159-63. https://doi.org/10.1007/s11060-011-0573-x
  14. Parkin DM, Bray F (2009). Evaluation of data quality in the cancer registry: principles and methods Part II. Completeness. Eur J Cancer, 45, 756-64. https://doi.org/10.1016/j.ejca.2008.11.033
  15. Polednak AP (2003). Trends in survival for both histologic types of esophageal cancer in US surveillance, epidemiology and end results areas. Int J Cancer, 105, 98-100. https://doi.org/10.1002/ijc.11029
  16. Romanuik TL, Wang G, Holt RA, et al (2009). Identification of novel androgen-responsive genes by sequencing of Long SAGE libraries. BMC Genomics, 10, 476. https://doi.org/10.1186/1471-2164-10-476
  17. Scott KL, Chin L (2010). Signaling from the Golgi: mechanisms and models for Golgi phosphoprotein 3-mediated oncogenesis. Clin Cancer Res, 16, 2229-34. https://doi.org/10.1158/1078-0432.CCR-09-1695
  18. Scott KL, Kabbarah O, Liang MC, et al (2009). GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer. Nature, 459, 1085-90. https://doi.org/10.1038/nature08109
  19. Wang JH, Chen XT, Wen ZS, et al (2012).High expression of GOLPH3 in esophageal squamous cell carcinoma correlates with poor prognosis. PLoS One, 7, e45622. https://doi.org/10.1371/journal.pone.0045622
  20. Wan QL, Hou XS, Zhao G (2013). Utility of serum peptidome patterns of esophageal squamous cell carcinoma patients for comprehensive treatment. Asian Pac J Cancer Prev, 14, 2919-23. https://doi.org/10.7314/APJCP.2013.14.5.2919
  21. Wood CS, Schmitz KR, Bessman NJ, et al (2009). PtdIns4P recognition by Vps74/GOLPH3 links PtdIns 4-kinase signaling to retrograde Golgi trafficking. J Cell Biol, 187, 967-75. https://doi.org/10.1083/jcb.200909063
  22. Zeng Z, Lin H, Zhao X, et al (2012).Overexpression of GOLPH3 promotes proliferation and tumorigenicity in breast cancer via suppression of the FOXO1 transcription factor. Clin Cancer Res, 18, 4059-69. https://doi.org/10.1158/1078-0432.CCR-11-3156
  23. Zhou X, Zhan W, Bian W, et al (2013). GOLPH3 regulates the migration and invasion of glioma cells though RhoA. Biochem Biophys Res Commun, 433, 338-44. https://doi.org/10.1016/j.bbrc.2013.03.003

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