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1.
Hepatology ; 73(5): 1797-1815, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33058300

RESUMO

BACKGROUND AND AIMS: Trimethylation of Lys36 on histone 3 (H3K36me3) catalyzed by histone methyltransferase SET domain-containing 2 (SETD2) is one of the most conserved epigenetic marks from yeast to mammals. SETD2 is frequently mutated in multiple cancers and acts as a tumor suppressor. APPROACH AND RESULTS: Here, using a liver-specific Setd2 depletion model, we found that Setd2 deficiency is sufficient to trigger spontaneous HCC. Meanwhile, Setd2 depletion significantly increased tumor and tumor size of a diethylnitrosamine-induced HCC model. The mechanistic study showed that Setd2 suppresses HCC not only through modulating DNA damage response, but also by regulating lipid metabolism in the liver. Setd2 deficiency down-regulated H3K36me3 enrichment and expression of cholesterol efflux genes and caused lipid accumulation. High-fat diet enhanced lipid accumulation and promoted the development of HCC in Setd2-deficient mice. Chromatin immunoprecipitation sequencing analysis further revealed that Setd2 depletion induced c-Jun/activator protein 1 (AP-1) activation in the liver, which was trigged by accumulated lipid. c-Jun acts as an oncogene in HCC and functions through inhibiting p53 in Setd2-deficient cells. CONCLUSIONS: We revealed the roles of Setd2 in HCC and the underlying mechanisms in regulating cholesterol homeostasis and c-Jun/AP-1 signaling.


Assuntos
Carcinoma Hepatocelular/etiologia , Histona-Lisina N-Metiltransferase/deficiência , Metabolismo dos Lipídeos , Neoplasias Hepáticas/etiologia , Fígado/metabolismo , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Proteína 9 Associada à CRISPR , Sistemas CRISPR-Cas , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Colesterol/sangue , Imunoprecipitação da Cromatina , Edição de Genes , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Células Hep G2 , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Triglicerídeos/sangue
2.
Huan Jing Ke Xue ; 37(11): 4247-4254, 2016 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-29964677

RESUMO

Three-dimensional ordered mesoporous Co3O4 was prepared by nanocasting method with porous silicon KIT-6 as the hard template and firstly used to activate peroxymonosulfate for the degradation of rhodamine B. The structural properties were characterized by BET, H-TEM, XRD, XPS, FT-IR. The results showed that three-dimensional ordered mesoporous Co3O4 presented far superior catalytic activity over conventional nanoscale Co3O4 due to its abundant space mesoporous channel structure and the large specific surface areas. Higher catalyst dosage and higher peroxymonosulfate concentration favored the decolorization of rhodamine B. The removal of rhodamine B could be accelerated in the presence of Cl- and H2PO4-; however, the decolorization of rhodamine B would be inhibited in the presence of NO3-, SO42- and HCO3-. Sulfate radicals were identified as the dominant active species for the decolorization of rhodamine B through radicals quenching experiments. Three-dimensional ordered mesoporous Co3O4 showed excellent catalytic activity even after five consecutive cycles.

3.
Zhonghua Yi Xue Za Zhi ; 85(43): 3035-8, 2005 Nov 16.
Artigo em Chinês | MEDLINE | ID: mdl-16324401

RESUMO

OBJECTIVE: To investigate the clinicopathologic features of and appropriate treatment of ductal carcinoma in situ of the breast (DCIS). METHODS: The clinical and pathologic data of 41 cases of DCIS, aged 52.7 (30-82), 15 of which were diagnosed as with ductal carcinoma in situ with microinvasion (DCIS-MI) and of which 18 were in the Van Nuys grade I, 13 in the grade II, and 10 in the grade III, were collected and analyzed. Immunohistochemical analysis was performed to examine the expressions of estrogen receptor (ER), progesterone receptor (PR), proliferating cell nuclear antigen (PCNA), P53 and C-erbB-2. RESULTS: Microinvasion was correlated with the histologic categories (chi(2) = 4.60, P < 0.05) and tumor size (chi(2) = 9.78, P < 0.05) significantly. The expression rates of ER, PR, PCNA, P53, and C-erbB-2 were 68.3%, 65.9%, 63.4%, 26.8%, and 46.3%, respectively. There was no significant difference in the expression of the biologic markers between the patients with DCIS and those with DCIS-MI. The expression levels of ER, P53, and C-erbB-2 were correlated with the histologic categories significantly (chi(2) = 11.45, 11.97, 4.38, P < 0.05). CONCLUSION: The Van Nuys histologic classification accords with the requirement of clinical treatment and prognosis. The patients with DCIS should undergo individualized treatment.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/metabolismo , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/biossíntese , Receptores de Estrogênio/biossíntese , Estudos Retrospectivos , Proteína Supressora de Tumor p53/biossíntese
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