RESUMO
BACKGROUND: Jumonji AT-rich interactive domain 1B(JARID1B) has been shown to be upregulated in many human cancers and plays a critical role in the development of cancers cells. Nevertheless, its functional role in colorectal cancer (CRC) progression is not fully understood. METHODS: Herein, JARID1B expression levels were detected in clinical CRC samples by western blotting and qRT-PCR. DLD-1 cells with JARID1B knockdown or overexpression by stably transfected plasmids were used in vitro and in vivo study. Colony formation, 5-ethynyl-20-deoxyuridine (EdU) and Real Time Cellular Analysis (RTCA) assays were used to detect cell proliferation and growth. Transcriptome and CHIP assays were used to examine the molecular biology changes and molecular interaction in these cells. Nude mice was utilized to study the correlation of JARID1B and tumor growth in vivo. RESULTS: Here, we first observed that JARID1B was significantly upregulated in CRC tissue compared to adjacent normal tissues. In CRC patients, JARID1B high expression was positively relation with poor overall survival. Multivariate analyses revealed that high JARID1B expression was an independent predictive marker for the poor prognosis of CRC. In addition, we found that JARID1B promoted CRC cells proliferation by Wnt/ß-catenin signaling pathway. Further studies demonstrated CDX2 as a downstream target of JARID1B, and our data demonstrated that CDX2 is crucial for JARID1B -mediated Wnt/ß-catenin signaling pathway. Mechanistically, we demonstrated that JARID1B regulated CDX2 expression through demethylation of H3K4me3. CONCLUSIONS: CDX2 inhibited by JARID1B-derived H3K4me3 methylation promoted cells proliferation of CRC via Wnt/ß-catenin signaling pathway. Therefore, our studies provided a novel insight into the role of JARID1B in CRC cells proliferation and potential new molecular target for treating CRC. Video abstract.
Assuntos
Fator de Transcrição CDX2/metabolismo , Neoplasias Colorretais/patologia , Histona Desmetilases com o Domínio Jumonji/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Repressoras/metabolismo , Via de Sinalização Wnt , Animais , Fator de Transcrição CDX2/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/genética , Progressão da Doença , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Histonas/metabolismo , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Lisina/metabolismo , Masculino , Metilação , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Análise Multivariada , Proteínas Nucleares/genética , Regiões Promotoras Genéticas/genética , Proteínas Repressoras/genética , Análise de Sobrevida , Regulação para Cima/genéticaRESUMO
Solitary necrotic nodule of the liver (SNNL) is an uncommon disease in clinical practice, and its pathogenesis is still unclear. Here, we report the case of a 35-year-old woman. After physical examination, the patient was found to have a liver neoplasm, and there were no other physical complaints. Abdominal contrast-enhanced computed tomography (CT) showed the presence of a hypodense lesion. The patient opted for surgery to eliminate the lesion. Pathologic examination revealed an isolated necrotic nodular lesion with a size of 12 cm×10 cm×10 cm. The patient had a history of hepatitis B infection. To our knowledge, this is the largest SNNL ever reported and the first case with a history of hepatitis B infection.