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A study of gene expression of survivin, its antiapoptotic variants, and targeting survivin in vitro for therapy in retinoblastoma

Samuel, Jaisy, Kanwar, Rupinder K., Kanwar, Jagat R., Khetan, Vikas M.D. and Krishnakumar, Subramanian M.D. 2016, A study of gene expression of survivin, its antiapoptotic variants, and targeting survivin in vitro for therapy in retinoblastoma, Journal of pediatric hematology/oncology, vol. 38, no. 7, pp. e230-e242, doi: 10.1097/MPH.0000000000000605.


Title A study of gene expression of survivin, its antiapoptotic variants, and targeting survivin in vitro for therapy in retinoblastoma
Author(s) Samuel, Jaisy
Kanwar, Rupinder K.
Kanwar, Jagat R.
Khetan, Vikas M.D.
Krishnakumar, Subramanian M.D.
Journal name Journal of pediatric hematology/oncology
Volume number 38
Issue number 7
Start page e230
End page e242
Total pages 13
Publisher Wolters Kluwer
Place of publication Philadelphia, Pa.
Publication date 2016-10
ISSN 1536-3678
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Oncology
Hematology
Pediatrics
retinoblastoma
apoptosis
survivin splice variants
Bcl-2
survivin-dominant negative mutant
Summary Apoptosis is a natural process regulated by apoptotic and antiapoptotic molecules. We investigated mRNA expression of survivin and its splice variants, along with B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax), in a cohort of 20 retinoblastoma (RB) tumors by real-time polymerase chain reaction. We hypothesized a correlation between the Bcl-2/Bax and survivin splice variants and also that expression of these would be associated with clinicopathologic features of tumors. The Bcl-2 expression was significantly higher (P<0.001) in RB, and Bcl-2/Bax ratio was remarkably higher in poorly differentiated tumors. A statistically significant higher expression of Survivin-WT (wild type) compared with its variant Survivin-2β (P<0.05) was observed. Bcl-2 did not exhibit positive correlation with any of the survivin variants except Survivin-2β, whereas Bax exhibited significant (P<0.05) correlation with the variants. Thus, it could be suggested that a superior player out of a likely interaction between the variants and Bcl-2/Bax uses its activity for the progression of RB. Silencing of Survivin-WT in the Y79 cell line was studied by siRNA technology and cell-permeable dominant negative survivin (SurR9-C84A). siRNA showed higher proapoptotic effects and increased caspase 3/7 activity in Y79 cells. Effective internalization of SurR9-C84A in Y79 cells induced cytotoxic effects. Thus, the current study confirms survivin as a promising target for therapy.
Language eng
DOI 10.1097/MPH.0000000000000605
Field of Research 110299 Cardiorespiratory Medicine and Haematology not elsewhere classified
1102 Cardiovascular Medicine And Haematology
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, Wolters Kluwer Health
Persistent URL http://hdl.handle.net/10536/DRO/DU:30087416

Document type: Journal Article
Collection: School of Medicine
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