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International Journal of Oncology
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Article

RNA interference-mediated knockdown of Livin suppresses cell proliferation and invasion and enhances the chemosensitivity to cisplatin in human osteosarcoma cells

  • Authors:
    • Xu Li
    • Shuli Fan
    • Leiming Li
    • Liguo Wang
    • Guangyu Fan
    • Qun Zhao
    • Yan Li
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, Liaoning 110004, P.R. China
  • Pages: 159-168
    |
    Published online on: April 30, 2013
       https://doi.org/10.3892/ijo.2013.1925
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Abstract

Livin is a novel member of the inhibitor of apoptosis protein (IAP) family that has been reported to be overexpressed in a variety of human malignancies, including osteosarcoma. However, the potential roles of Livin in tumorigenesis have not been elucidated. In the present study, we employed RNA interference (RNAi) technology to suppress endogenous Livin expression in osteosarcoma cells and successfully generated a U2-OS cell line with stably knockdown of Livin. Functional analysis showed that knockdown of Livin significantly reduced cell proliferation, colony formation, and invasion and migration capacities of U2-OS cells in vitro. Moreover, specific downregulation of Livin led to cell cycle arrest at the G0/G1 phase and eventual apoptosis. Meanwhile, western blot analysis revealed that cells with stably knockdown of Livin showed decreased expression levels of Cyclin D1, Bcl-2, matrix metalloproteinase (MMP)-2 and MMP-9, but increased expression levels of activated Caspase-3, Bax and cleaved poly (ADP-ribose) polymerase (PARP) compared to those transfected with a control vector. We also observed that suppression of Livin expression in osteosarcoma cells increased their chemosensitivity to cisplatin. Taken together, our data suggest that Livin is involved in tumorigenesis of human osteosarcoma and may serve as a promising therapeutic target for osteosarcoma.
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1. 

Ottaviani G and Jaffe N: The epidemiology of osteosarcoma. Cancer Treat Res. 152:3–13. 2009. View Article : Google Scholar

2. 

Chou AJ and Gorlick R: Chemotherapy resistance in osteosarcoma: current challenges and future directions. Expert Rev Anticancer Ther. 6:1075–1085. 2006. View Article : Google Scholar : PubMed/NCBI

3. 

Fuchs B and Pritchard DJ: Etiology of osteosarcoma. Clin Orthop Relat Res. 397:40–52. 2002. View Article : Google Scholar

4. 

Akiyama T, Dass CR and Choong PF: Novel therapeutic strategy for osteosarcoma targeting osteoclast differentiation, bone-resorbing activity, and apoptosis pathway. Mol Cancer Ther. 7:3461–3469. 2008. View Article : Google Scholar : PubMed/NCBI

5. 

Salvesen GS and Duckett CS: IAP proteins: blocking the road to death’s door. Nat Rev Mol Cell Biol. 3:401–410. 2002.

6. 

Chang H and Schimmer AD: Livin/melanoma inhibitor of apoptosis protein as a potential therapeutic target for the treatment of malignancy. Mol Cancer Ther. 6:24–30. 2007. View Article : Google Scholar : PubMed/NCBI

7. 

Liston P, Fong WG and Korneluk RG: The inhibitors of apoptosis: there is more to life than Bcl2. Oncogene. 22:8568–8580. 2003. View Article : Google Scholar : PubMed/NCBI

8. 

Nachmias B, Ashhab Y and Ben-Yehuda D: The inhibitor of apoptosis protein family (IAPs): an emerging therapeutic target in cancer. Semin Cancer Biol. 14:231–243. 2004. View Article : Google Scholar : PubMed/NCBI

9. 

Schimmer AD: Inhibitor of apoptosis proteins: translating basic knowledge into clinical practice. Cancer Res. 64:7183–7190. 2004. View Article : Google Scholar : PubMed/NCBI

10. 

Gazzaniga P, Gradilone A, Giuliani L, et al: Expression and prognostic significance of LIVIN, SURVIVIN and other apoptosis-related genes in the progression of superficial bladder cancer. Ann Oncol. 14:85–90. 2003. View Article : Google Scholar : PubMed/NCBI

11. 

Xi RC, Sheng YR, Chen WH, et al: Expression of survivin and livin predicts early recurrence in non-muscle invasive bladder cancer. J Surg Oncol. 107:550–554. 2013. View Article : Google Scholar : PubMed/NCBI

12. 

Tanabe H, Yagihashi A, Tsuji N, Shijubo Y, Abe S and Watanabe N: Expression of survivin mRNA and livin mRNA in non-small-cell lung cancer. Lung Cancer. 46:299–304. 2004. View Article : Google Scholar : PubMed/NCBI

13. 

Xiang Y, Yao H, Wang S, et al: Prognostic value of Survivin and Livin in nasopharyngeal carcinoma. Laryngoscope. 116:126–130. 2006. View Article : Google Scholar : PubMed/NCBI

14. 

Kempkensteffen C, Hinz S, Christoph F, et al: Expression of the apoptosis inhibitor livin in renal cell carcinomas: correlations with pathology and outcome. Tumour Biol. 28:132–138. 2007. View Article : Google Scholar : PubMed/NCBI

15. 

Augello C, Caruso L, Maggioni M, et al: Inhibitors of apoptosis proteins (IAPs) expression and their prognostic significance in hepatocellular carcinoma. BMC Cancer. 9:1252009. View Article : Google Scholar : PubMed/NCBI

16. 

Dasgupta A, Alvarado CS, Xu Z and Findley HW: Expression and functional role of inhibitor-of-apoptosis protein livin (BIRC7) in neuroblastoma. Biochem Biophys Res Commun. 400:53–59. 2010. View Article : Google Scholar : PubMed/NCBI

17. 

Xi RC, Biao WS and Gang ZZ: Significant elevation of survivin and livin expression in human colorectal cancer: inverse correlation between expression and overall survival. Onkologie. 34:428–432. 2011. View Article : Google Scholar : PubMed/NCBI

18. 

Lazar I, Perlman R, Lotem M, Peretz T, Ben-Yehuda D and Kadouri L: The clinical effect of the inhibitor of apopotosis protein livin in melanoma. Oncology. 82:197–204. 2012. View Article : Google Scholar : PubMed/NCBI

19. 

Liang YZ, Fang TY, Xu HG and Zhuo ZQ: Expression of CD44v6 and Livin in gastric cancer tissue. Chin Med J (Engl). 125:3161–3165. 2012.PubMed/NCBI

20. 

Yu L and Wang Z: Effects of Livin gene RNA interference on apoptosis of cervical cancer HeLa cells and enhanced sensitivity to cisplatin. J Huazhong Univ Sci Technolog Med Sci. 29:625–630. 2009. View Article : Google Scholar : PubMed/NCBI

21. 

Wang TS, Ding QQ, Guo RH, et al: Expression of livin in gastric cancer and induction of apoptosis in SGC-7901 cells by shRNA-mediated silencing of livin gene. Biomed Pharmacother. 64:333–338. 2010. View Article : Google Scholar : PubMed/NCBI

22. 

Yang D, Song X, Zhang J, et al: Therapeutic potential of siRNA-mediated combined knockdown of the IAP genes (Livin, XIAP, and Survivin) on human bladder cancer T24 cells. Acta Biochim Biophys Sin (Shanghai). 42:137–144. 2010. View Article : Google Scholar

23. 

Wang X, Xu J, Ju S, Ni H, Zhu J and Wang H: Livin gene plays a role in drug resistance of colon cancer cells. Clin Biochem. 43:655–660. 2010. View Article : Google Scholar : PubMed/NCBI

24. 

Yang D, Song X, Zhang J, et al: Suppression of livin gene expression by siRNA leads to growth inhibition and apoptosis induction in human bladder cancer T24 cells. Biosci Biotechnol Biochem. 74:1039–1044. 2010. View Article : Google Scholar : PubMed/NCBI

25. 

Liu H, Wang S, Sun H, Pan Z, Zhou W and Wu M: Inhibition of tumorigenesis and invasion of hepatocellular carcinoma by siRNA-mediated silencing of the livin gene. Mol Med Rep. 3:903–907. 2010.PubMed/NCBI

26. 

Yuan B, Ran B, Wang S, Liu Z, Zheng Z and Chen H: siRNA directed against Livin inhibits tumor growth and induces apoptosis in human glioma cells. J Neurooncol. 107:81–87. 2012. View Article : Google Scholar : PubMed/NCBI

27. 

Chen F, Yang D, Wang S, et al: Livin regulates prostate cancer cell invasion by impacting the NF-kappaB signaling pathway and the expression of FN and CXCR4. IUBMB Life. 64:274–283. 2012. View Article : Google Scholar : PubMed/NCBI

28. 

Liu X, Wang A, Gao H, Yuan Z and Jiao Y: Expression and role of the inhibitor of apoptosis protein livin in chemotherapy sensitivity of ovarian carcinoma. Int J Oncol. 41:1021–1028. 2012.PubMed/NCBI

29. 

Nedelcu T, Kubista B, Koller A, et al: Livin and Bcl-2 expression in high-grade osteosarcoma. J Cancer Res Clin Oncol. 134:237–244. 2008. View Article : Google Scholar : PubMed/NCBI

30. 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

31. 

Li Y, Li X, Fan G, et al: Impairment of p53 acetylation by EWS-Fli1 chimeric protein in Ewing family tumors. Cancer Lett. 320:14–22. 2012. View Article : Google Scholar : PubMed/NCBI

32. 

Chen F, Yang D, Che X, et al: Livin mediates tumor cell invasion in the DU-145 cell line via NF-κB. Oncol Rep. 27:2010–2016. 2012.PubMed/NCBI

33. 

Yuan D, Liu L, Xu H and Gu D: The effects on cell growth and chemosensitivity by livin RNAi in non-small cell lung cancer. Mol Cell Biochem. 320:133–140. 2009. View Article : Google Scholar : PubMed/NCBI

34. 

Ding ZY, Liu GH, Olsson B and Sun XF: Upregulation of the antiapoptotic factor Livin contributes to cisplatin resistance in colon cancer cells. Tumour Biol. 34:683–693. 2013. View Article : Google Scholar : PubMed/NCBI

35. 

Wang H, Tan SS, Wang XY, et al: Silencing livin gene by siRNA leads to apoptosis induction, cell cycle arrest, and proliferation inhibition in malignant melanoma LiBr cells. Acta Pharmacol Sin. 28:1968–1974. 2007. View Article : Google Scholar : PubMed/NCBI

36. 

Wang R, Lin F, Wang X, et al: Silencing Livin gene expression to inhibit proliferation and enhance chemosensitivity in tumor cells. Cancer Gene Ther. 15:402–412. 2008. View Article : Google Scholar : PubMed/NCBI

37. 

Ye L, Song X, Li S, et al: Livin-alpha promotes cell proliferation by regulating G1-S cell cycle transition in prostate cancer. Prostate. 71:42–51. 2011. View Article : Google Scholar : PubMed/NCBI

38. 

Chen YS, Li HR, Miao Y, et al: Local injection of lentivirus-delivered livinshRNA suppresses lung adenocarcinoma growth by inducing a G0/G1 phase cell cycle arrest. Int J Clin Exp Pathol. 5:796–805. 2012.PubMed/NCBI

39. 

Bauvois B: New facets of matrix metalloproteinases MMP-2 and MMP-9 as cell surface transducers: outside-in signaling and relationship to tumor progression. Biochim Biophys Acta. 1825:29–36. 2012.PubMed/NCBI

40. 

Tabruyn SP and Griffioen AW: A new role for NF-kappaB in angiogenesis inhibition. Cell Death Differ. 14:1393–1397. 2007. View Article : Google Scholar : PubMed/NCBI

41. 

Ma D, Tremblay P, Mahngar K, Collins J, Hudlicky T and Pandey S: Selective cytotoxicity against human osteosarcoma cells by a novel synthetic C-1 analogue of 7-deoxypancratistatin is potentiated by curcumin. PLoS One. 6:e287802011. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Li X, Fan S, Li L, Wang L, Fan G, Zhao Q and Li Y: RNA interference-mediated knockdown of Livin suppresses cell proliferation and invasion and enhances the chemosensitivity to cisplatin in human osteosarcoma cells. Int J Oncol 43: 159-168, 2013.
APA
Li, X., Fan, S., Li, L., Wang, L., Fan, G., Zhao, Q., & Li, Y. (2013). RNA interference-mediated knockdown of Livin suppresses cell proliferation and invasion and enhances the chemosensitivity to cisplatin in human osteosarcoma cells. International Journal of Oncology, 43, 159-168. https://doi.org/10.3892/ijo.2013.1925
MLA
Li, X., Fan, S., Li, L., Wang, L., Fan, G., Zhao, Q., Li, Y."RNA interference-mediated knockdown of Livin suppresses cell proliferation and invasion and enhances the chemosensitivity to cisplatin in human osteosarcoma cells". International Journal of Oncology 43.1 (2013): 159-168.
Chicago
Li, X., Fan, S., Li, L., Wang, L., Fan, G., Zhao, Q., Li, Y."RNA interference-mediated knockdown of Livin suppresses cell proliferation and invasion and enhances the chemosensitivity to cisplatin in human osteosarcoma cells". International Journal of Oncology 43, no. 1 (2013): 159-168. https://doi.org/10.3892/ijo.2013.1925
Copy and paste a formatted citation
x
Spandidos Publications style
Li X, Fan S, Li L, Wang L, Fan G, Zhao Q and Li Y: RNA interference-mediated knockdown of Livin suppresses cell proliferation and invasion and enhances the chemosensitivity to cisplatin in human osteosarcoma cells. Int J Oncol 43: 159-168, 2013.
APA
Li, X., Fan, S., Li, L., Wang, L., Fan, G., Zhao, Q., & Li, Y. (2013). RNA interference-mediated knockdown of Livin suppresses cell proliferation and invasion and enhances the chemosensitivity to cisplatin in human osteosarcoma cells. International Journal of Oncology, 43, 159-168. https://doi.org/10.3892/ijo.2013.1925
MLA
Li, X., Fan, S., Li, L., Wang, L., Fan, G., Zhao, Q., Li, Y."RNA interference-mediated knockdown of Livin suppresses cell proliferation and invasion and enhances the chemosensitivity to cisplatin in human osteosarcoma cells". International Journal of Oncology 43.1 (2013): 159-168.
Chicago
Li, X., Fan, S., Li, L., Wang, L., Fan, G., Zhao, Q., Li, Y."RNA interference-mediated knockdown of Livin suppresses cell proliferation and invasion and enhances the chemosensitivity to cisplatin in human osteosarcoma cells". International Journal of Oncology 43, no. 1 (2013): 159-168. https://doi.org/10.3892/ijo.2013.1925
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