A Study of Gene Expression of Survivin, its Antiapoptotic Variants, and Targeting Survivin In Vitro for Therapy in Retinoblastoma

Abstract

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.

Comparative analysis of pathophysiological parameters between emphysematous smokers and emphysematous patients with COPD

“…Moreover, the expression of Bcl-2, another anti-apoptotic factor, was relatively higher in emphysematous smokers than that in emphysematous patients with COPD. Studies have confirmed Bcl-2 expression does not correlate with Survivin expression, which may also explain the relatively higher expression of Survivin in patients with COPD 30 .…”

Construction of a Functional Nucleic Acid-Based Artificial Vesicle-Encapsulated Composite Nanoparticle and Its Application in Retinoblastoma-Targeted Theranostics

“…In the continued study on genomics and pathogenesis of RB, the regulation and intervention targeting the key gene of RB has become a new strategy for RB treatment. Studies have shown that B-cell lymphoma 2 (Bcl-2) and Survivin (Svv) mRNAs are overexpressed in RB cells, suggesting that these two mRNAs might be promising therapeutic targets. , In particular, the eye offers certain anatomical advantages as a target tissue, which is conducive to the development of multifunctional diagnostic nanocontrast agents combining anti-RB gene therapeutic agents with multimodal imaging technology. Currently, the agents mainly used for RB gene therapy are small interfering RNA (siRNA). , However, compared to DNA gene therapeutic agents, RNA is less stable and exhibits lower enzymatic degradation resistance .…”

“…Studies have shown that B-cell lymphoma 2 (Bcl-2) and Survivin (Svv) mRNAs are overexpressed in RB cells, suggesting that these two mRNAs might be promising therapeutic targets. 3,4 In particular, the eye offers certain anatomical advantages as a target tissue, which is conducive to the development of multifunctional diagnostic nanocontrast agents combining anti-RB gene therapeutic agents with multimodal imaging technology. Currently, the agents mainly used for RB gene therapy are small interfering RNA (siRNA).…”