Survivin-directed RNA interference is a potent suppressor of leukemia growth

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 17590986
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: University of Fukui
• Principal Investigator: YOSHIDA Akira University of Fukui, University of Fukui Hospital, Associate Professor (80252005)
• Project Period (FY): 2005 – 2007
• Keywords: Apoptosis / Survivin-3B / Leukemia / medical treatment

Research Abstract

Survivin, a new member of the inhibitor of apoptosis protein (IAP) family, has been reported to be expressed in cancers. We identified a novel splice variant of survivin, designated as survivin-3B (accession No.AB154416). It comprises 5 exons including novel exon 3B derived from a 165-bp long portion of intron 3. It contains a single bacurovirus IAP repeat (BIR). Expression of survivin-3B was detected in human colon and gastric adenocarcinoma cell lines as well as samples from patients with myelodysplastic syndrome and acute leukemia. However, biological role of survivin-3B remains unclear. We performed experiments to examine its function. Overexpression of survivin-3B in leukemia and colon cancer cells reduced cell death after etoposide and cispla tin treatment, suggesting its anti-apoptotic property. Four types of short h airpin RNAs (shRNAs) (#1#4) were designed, targeting both survivin itself and survivin-3B. The lentivirus-mediated shRNA delivery strongly suppressed H L-60 leukemia growth. These data indicate that survivin-3B possesses anti-apoptotic function. Both survivin-3B and survivin-directed RNA interference is a potent suppressor of leukemia growth.

Research Products

• [Journal Article] GP7 induces internucleosomal DNA fragmentation independent of caspase activation and DNA fragmentation factor in NB4 cells. (2007)
  • Author(s): Qi SN, Jing YX, Dong GX, Chen Y, Yoshida A, Ueda T.
  • Journal Title: Oncol Rep. 18(1) Pages: 273-277
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] GP7 induces internucleosomal DNA fragmentation independent of caspase activation and DNA fragmentation factor in NB4 cells (2007)
  • Author(s): Qi, SN, Sing, YX., Dong, GX., Chen, Y., Yoshida, A., Ueda, T
  • Journal Title: Oncol Rep 18(1) Pages: 273-277
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Endonuclease activation and chromosomal DNA fragmentation during apoptosis in leukemia cells. (2006)
  • Author(s): Yoshida A, Pommier Y, Ueda T.
  • Journal Title: Int J Hematol. 84 Pages: 31-37
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Inhibition of glutathione synthesis overcomes Bcl-2-mediated topoisomerase inhibitor resistance and induces nonapoptotic cell death via mitochondrial-independent pathway. (2006)
  • Author(s): Yoshida A^*, Takemura H, Inoue H, Miyashita T, Ueda T.
  • Journal Title: Cancer Res. 66 Pages: 5772-5780
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Endonuclease activation and chromosomal DNA fragmentation during apoptosis In leukemia cells (2006)
  • Author(s): Yoshida, A., Pozmnier, Y., Ueda, T
  • Journal Title: Int J Hematol 84 Pages: 31-37
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibition of glutathione synthesis overcomes Bcl-2-mediated topoisomerase inhibitor resistance and induces nonapoptotic cell death viamitochondrial-independent pathway (2006)
  • Author(s): Yoshida, A*., Takemura, H., Inoue, H., Miyashita, T., Ueda, T
  • Journal Title: Cancer Res 66 Pages: 5772-5780
  • Description: 「研究成果報告書概要(欧文)」より