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1.
Biochem Biophys Res Commun ; 669: 19-29, 2023 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-37262949

RESUMO

ASH2L (Absent-Small-Homeotic-2-Like protein) is a core subunit of the COMPASS (COMplex of Proteins ASsociated with Set1) complex, the most notable writer of the methylation of histone H3 lysine 4 (H3K4). The COMPASS complex regulates active promoters or enhancers for gene expression, and its dysfunction is associated with aberrant development and disease. Here, we demonstrated that ASH2L mediated the cell invasion and migration activity of triple-negative breast cancer cells through the interaction with the COMPASS components and the target genomic regions. Transcriptome analysis indicated a potential correlation between ASH2L and the genes involved in inflammatory/immune responses. Among them, we found that the intrinsic expression of IL1B (interleukin 1 beta), an essential proinflammatory gene, was directly regulated by ASH2L. These results revealed a novel role of ASH2L on the maintenance of breast cancer malignancy possibly through H3K4 methylation of the target inflammatory/immune responsive genes.


Assuntos
Histonas , Neoplasias de Mama Triplo Negativas , Humanos , Histonas/metabolismo , Metilação , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Lisina/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Epigênese Genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
2.
Biochem Biophys Res Commun ; 524(1): 150-155, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-31982139

RESUMO

N6-Methyladenosine (m6A) is the most common internal chemical modification of mRNAs involved in many pathological processes including various cancers. In this study, we investigated the role of m6A methyltransferase METTL3 in TGF-ß-induced epithelial-mesenchymal transition (EMT) of lung cancer cell lines. The expression of METTL3 and m6A RNA modification were increased during TGF-ß-induced EMT of A549 and LC2/ad lung cancer cells. Knockdown of METTL3 inhibited TGF-ß-induced morphological conversion of the cells, enhanced cell migration potential and the expression changes of EMT-related marker genes such as CDH1/E-cadherin, FN1/Fibronectin and VIM/Vimentin. Mechanistic investigations revealed that METTL3 knockdown decreased the m6A modification, total mRNA level and mRNA stability of JUNB, one of the important transcriptional regulators of EMT. Over-expression of JUNB partially rescued the inhibitory effects of METTL3 knockdown in the EMT phenotypes. This study demonstrates that m6A methyltransferase METTL3 is indispensable for TGF-ß-induced EMT of lung cancer cells through the regulation of JUNB.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Metiltransferases/metabolismo , Fatores de Transcrição/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/genética , Metiltransferases/genética , Fenótipo , Estabilidade de RNA/efeitos dos fármacos , Fatores de Transcrição/genética
3.
Chinese Journal of School Health ; (12): 834-838, 2022.
Artigo em Chinês | WPRIM | ID: wpr-934809

RESUMO

Objective@#To explore character strengths of college students who sought counseling, and its relationship with mental health.@*Methods@#A total of 180 college students who sought counseling were investigated by using the short version of Character Strengths Questionnaire and the Symptom Checklist 90 (SCL-90) during March 2020 to October 2021.@*Results@#The top five character strengths of college students who sought counseling were appreciation, authenticity, gratitude, humor, love of learning ( 8.39± 1.64, 7.82±1.74, 7.73±1.57, 7.29±1.81, 7.17±1.88); The bottom five character strengths were kindness, bravery, persistence, zest, leadership (5.59±1.75, 5.81±1.30, 5.86±1.72, 5.98±1.59, 6.06±1.60). Linear regression analysis found love, social intelligence and insight showed associations with different dimensions of mental health, with correlation coefficient of each regression equation between -0.12 and 0.16, and the coefficient of determination between 0.05 and 0.19 ( P <0.01). Love had a negativeassociation with all factors of SCL- 90 ( β=-0.314--0.159, P <0.05), which could explain 3.3%-12.5% of the variation of each factor. Social intelligence had a negative association with obsessive compulsive, interpersonal sensitivity and anxiety ( β=-0.200--0.150, P <0.05), which can explain 1.6%-3.2% of the variation. Insight had a positive association with somatization, hostility and paranoia ( β=0.168-0.279, P <0.05), which can explain 2.3%-3.8% of the variation.@*Conclusion@#The lack and excess of character strengths is associated with mental health problems. Therefore, it would be more effective to help counseling cases build an appropriate and balanced character in the context of a strengths based approach.

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