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1.
Neuroscience Bulletin ; (6): 1087-1104, 2023.
Artículo en Inglés | WPRIM | ID: wpr-982458

RESUMEN

Gene transcription and new protein synthesis regulated by epigenetics play integral roles in the formation of new memories. However, as an important part of epigenetics, the function of chromatin remodeling in learning and memory has been less studied. Here, we showed that SMARCA5 (SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 5), a critical chromatin remodeler, was responsible for hippocampus-dependent memory maintenance and neurogenesis. Using proteomics analysis, we found protein expression changes in the hippocampal dentate gyrus (DG) after the knockdown of SMARCA5 during contextual fear conditioning (CFC) memory maintenance in mice. Moreover, SMARCA5 was revealed to participate in CFC memory maintenance via modulating the proteins of metabolic pathways such as nucleoside diphosphate kinase-3 (NME3) and aminoacylase 1 (ACY1). This work is the first to describe the role of SMARCA5 in memory maintenance and to demonstrate the involvement of metabolic pathways regulated by SMARCA5 in learning and memory.


Asunto(s)
Ratones , Animales , Memoria , Ensamble y Desensamble de Cromatina , Hipocampo/metabolismo , Factores de Transcripción/metabolismo , Cromatina/metabolismo , Redes y Vías Metabólicas
2.
Clinics ; 68(5): 652-657, maio 2013. tab, graf
Artículo en Inglés | LILACS | ID: lil-675750

RESUMEN

OBJECTIVE: The aim of this study is to verify the expression of proteins that are controlled by miR-let7c, 100 and 218 using immunohistochemistry in tissue microarray representative of localized and metastasized the lymph nodes and bone prostate cancer. METHODS: To verify the expression of proteins that are controlled by miR-let7c (C-MYC, BUB1, RAS) 100 (SMARCA5, RB) and 218 (LAMB3) and cell proliferation (Ki-67) we used immunohistochemistry and computerized image system ImageJ MacBiophotonics in three tissue microarrays representative of localized prostate cancer and lymph node and bone metastases. miRNA expression was evaluated by qRT-PCR using 60 paraffin blocks to construct the tissue microarray representative of localized disease. RESULTS: RAS expression was increased in localized prostate cancer and bone metastases compared to the lymph nodes (p=0.017). RB showed an increase in expression from localized prostate cancer to lymph node and bone metastasis (p=0.036). LAMB3 was highly expressed in localized and lymph node metastases (p<0.001). Cell proliferation evaluated by Ki-67 showed an increase from localized prostate cancer to metastases (p<0.001). We did not found any relationship between C-MYC (p=0.253), BUB1 (p=0.649) and SMARCA5 (p=0.315) protein expression with prognosis or tumor behavior. CONCLUSION: We found that the expression of RAS, RB, LAMB3 and Ki-67 changed in the different stages of prostate cancer. Furthermore, we confirmed the overexpression of the miRNAs let7c, 100 and 218 in localized prostate cancer but failed to show the control of protein expression by the putative controller miRNAs using immunohistochemistry. .


Asunto(s)
Adulto , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Óseas/secundario , MicroARNs/metabolismo , Proteínas de Neoplasias/fisiología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Adenosina Trifosfatasas/metabolismo , Moléculas de Adhesión Celular/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Regulación Neoplásica de la Expresión Génica , Inmunohistoquímica , /metabolismo , Metástasis Linfática , MicroARNs/genética , MicroARNs/fisiología , Proteínas de Neoplasias/metabolismo , Pronóstico , Neoplasias de la Próstata/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , /metabolismo , Proteína de Retinoblastoma/metabolismo
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