ArticleAdvanced pharmaceutical bulletin2025
GAS5 Long Noncoding RNA Regulates CD20 Expression and Rituximab Response.
Article in Advanced pharmaceutical bulletin, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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4 authors.
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Abstract
Purpose: Rituximab is the primary treatment for non-Hodgkin lymphoma (NHL), one of the most common cancers globally. One of the main challenges associated with rituximab therapy is the decline in its effectiveness over time. Several suggested potential reasons for this therapeutic resistance exist, including the downregulation of CD20 expression. Recently, the focus has shifted to long non-coding RNAs (lncRNAs) like growth arrest specific 5 (GAS5) for their involvement in various physiological functions and their potential role in the response rate to anticancer drugs. In this study, we aimed to investigate the regulatory effect of GAS5 on CD20 expression and the response of cancer cells to rituximab. Methods: Using the Raji cell model, we assessed the impact of GAS5 knockdown on CD20 expression and the response to rituximab through RT-qPCR assay. Western blot analysis, caspase-3 activity, and ROS assay were conducted to evaluate protein expression levels, apoptosis, and oxidative stress, respectively. Results: In silico analysis predicted interactions between GAS5 and regulatory proteins associated with CD20. GAS5 knockdown increased CD20 and STAT3 expression while decreasing SMAD2 levels and apoptosis. It also reduced generation of reactive oxygen species (ROS) and enhanced autophagy. However, combining GAS5 knockdown with rituximab elevated apoptosis and autophagy while further reducing ROS. These findings suggest an indirect regulatory role for GAS5 in CD20 expression, potentially via modulation of CD20-associated regulatory proteins. Nonetheless, the study has limitations, including reliance on a single cell line and the assessment of direct apoptosis only. Conclusion: These findings highlight a complex interplay between GAS5, CD20, rituximab, and cellular pathways, underscoring the significance of understanding these interactions to enhance cancer therapy outcomes.
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