Oncogenic role of p53 is suppressed by si-RNA bicistronic construct of uPA, uPAR and cathepsin-B in meningiomas both in vitro and in vivo

Retraction in: /10.3892/ijo.2021.5186

  • Authors:
    • Reshu Gupta
    • Venkateswara Rao Gogineni
    • Arun Kumar Nalla
    • Chandramu Chetty
    • Jeffrey D. Klopfenstein
    • Andrew J. Tsung
    • Sanjeeva Mohanam
    • Jasti S. Rao
  • View Affiliations

  • Published online on: February 2, 2011     https://doi.org/10.3892/ijo.2011.934
  • Pages: 973-983
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Abstract

Meningiomas are the most commonly occurring intracranial tumors and account for approximately 15-20% of central nervous system tumors. Patients whose tumors recur after surgery and radiation therapy have limited therapeutic options. It has also been reported recently that radiation triggers DNA repair, cell survival and cell proliferation, and reduces apoptosis via the induction of cellular protective mechanisms. Earlier studies have reported that proteases such as uPA, uPAR and cathepsin B play important roles in tumor progression. In the present study, we attempted to determine the effectiveness of two bicistronic siRNA constructs pUC (uPAR/cathepsin B) and pU2 (uPA/uPAR) either alone or in combination with radiation, both in in vitro and in vivo models. Transfection of a plasmid vector expressing double-stranded RNA for uPA, uPAR and cathepsin B significantly induced the sub-G0-G1 cell population by the mitochondrial intrinsic apoptotic pathway. Results showed that pUC efficiently enhanced sub-G0-G1 phases compared to pU2 and was more effective. Interestingly, we observed that in IOMM-Lee cell lines, combined treatment of radiation with pUC and pU2 is more effective in comparison to SF-3061 and MN cell lines. We showed that apoptosis caused by these bicistronic constructs involves Bcl-2, Bcl-xL, p53 inactivation, cytochrome c release from mitochondria and caspase-9 activation, followed by the activation of caspase-3. We also determined that apoptosis caused by pUC and pU2 involves a mechanism which includes inactivation of p53 by its translocation from nucleus to cytoplasm as confirmed by immunofluorescence, which shows the oncogenic potential of p53 in meningiomas. However, the simultaneous RNAi-mediated targeting of uPAR and cathepsin B (pUC), in combination with irradiation, has greater potential application for the treatment of human meningioma in comparison to pU2 by decreasing p53 expression both in vitro and in vivo.

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April 2011
Volume 38 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Gupta R, Rao Gogineni V, Nalla AK, Chetty C, Klopfenstein JD, Tsung AJ, Mohanam S and Rao JS: Oncogenic role of p53 is suppressed by si-RNA bicistronic construct of uPA, uPAR and cathepsin-B in meningiomas both in vitro and in vivo Retraction in /10.3892/ijo.2021.5186. Int J Oncol 38: 973-983, 2011
APA
Gupta, R., Rao Gogineni, V., Nalla, A.K., Chetty, C., Klopfenstein, J.D., Tsung, A.J. ... Rao, J.S. (2011). Oncogenic role of p53 is suppressed by si-RNA bicistronic construct of uPA, uPAR and cathepsin-B in meningiomas both in vitro and in vivo Retraction in /10.3892/ijo.2021.5186. International Journal of Oncology, 38, 973-983. https://doi.org/10.3892/ijo.2011.934
MLA
Gupta, R., Rao Gogineni, V., Nalla, A. K., Chetty, C., Klopfenstein, J. D., Tsung, A. J., Mohanam, S., Rao, J. S."Oncogenic role of p53 is suppressed by si-RNA bicistronic construct of uPA, uPAR and cathepsin-B in meningiomas both in vitro and in vivo Retraction in /10.3892/ijo.2021.5186". International Journal of Oncology 38.4 (2011): 973-983.
Chicago
Gupta, R., Rao Gogineni, V., Nalla, A. K., Chetty, C., Klopfenstein, J. D., Tsung, A. J., Mohanam, S., Rao, J. S."Oncogenic role of p53 is suppressed by si-RNA bicistronic construct of uPA, uPAR and cathepsin-B in meningiomas both in vitro and in vivo Retraction in /10.3892/ijo.2021.5186". International Journal of Oncology 38, no. 4 (2011): 973-983. https://doi.org/10.3892/ijo.2011.934