RESUMO
OBJECTIVE: SUMO-specific protease 3 (SENP3), a member of the SUMO-specific protease family, reverses the SUMOylation of SUMO-2/3 conjugates. Dysregulation of SENP3 has been proven to be involved in the development of various tumors. However, its role in mantle cell lymphoma (MCL), a highly aggressive lymphoma, remains unclear. This study was aimed to elucidate the effect of SENP3 in MCL. METHODS: The expression of SENP3 in MCL cells and tissue samples was detected by RT-qPCR, Western blotting or immunohistochemistry. MCL cells with stable SENP3 knockdown were constructed using short hairpin RNAs. Cell proliferation was assessed by CCK-8 assay, and cell apoptosis was determined by flow cytometry. mRNA sequencing (mRNA-seq) was used to investigate the underlying mechanism of SENP3 knockdown on MCL development. A xenograft nude mouse model was established to evaluate the effect of SENP3 on MCL growth in vivo. RESULTS: SENP3 was upregulated in MCL patient samples and cells. Knockdown of SENP3 in MCL cells inhibited cell proliferation and promoted cell apoptosis. Meanwhile, the canonical Wnt signaling pathway and the expression of Wnt10a were suppressed after SENP3 knockdown. Furthermore, the growth of MCL cells in vivo was significantly inhibited after SENP3 knockdown in a xenograft nude mouse model. CONCLUSION: SENP3 participants in the development of MCL and may serve as a therapeutic target for MCL.
Assuntos
Linfoma de Célula do Manto , Adulto , Animais , Humanos , Camundongos , Apoptose/genética , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Modelos Animais de Doenças , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/patologia , Camundongos Nus , Proteínas do Tecido Nervoso , Peptídeo Hidrolases/uso terapêutico , RNA Mensageiro , Proteínas Wnt/uso terapêuticoRESUMO
Resveratrol, found in variety of plants, is a natural stilbene structure polyphenol. It has various pharmacological effects, such as antioxidation, anti-aging, anti-inflammation, anti-cancer, antiobesity, anti-diabetes, cardioprotection, neuroprotection. Recently, anti-leukemia activities of resveratrol has been studied extensively via its effects on a variety of biological processes involving cell proliferation, apoptosis, autophagy. Current treatments of leukemia mainly rely on intensive chemotherapy or hematopoietic stem cell transplantation, however, these treatments are still with poor survival and high treatment-related mortality. Therefore, it is extremely needed to find relatively non-toxic medicines with minimal side effects but sufficient therapeutic efficacy. Resveratrol is one such potential candidate owing to its reported anti-leukemia effect. In this review, we summarized resveratrol's discovery, sources and isolation methods, administration methods, effects in different types of leukemia, pharmacokinetics and toxicities, aiming to exploit resveratrol as a potential drug candidate for anti-leukemia.