RESUMO
BACKGROUND/AIMS: The tripartite motif containing (TRIM) family plays crucial roles in tumor development and progression. However, little is known about the function and mechanism of TRIM11 in hepatocellular carcinoma (HCC). METHODS: The expression levels of TRIM11 were examined by real-time PCR, Western blot and Immunohistochemical (IHC) staining. TRIM11 knockdown cells were produced by lentivirus infection, and functional assays, such as MTT, colony formation assay, migration and invasion assays and a xenograft tumor model were used to investigate the role of TRIM11 in HCC. We also determined the effect of TRIM11 on p53 signaling and its downstream molecules. RESULTS: We found that TRIM11 mRNA and protein levels were significantly increased in HCC tissues as compared with normal tissues; increased levels correlated with poor patient survival. By loss- and gain-of-function investigations, knockdown of TRIM11 suppressed cell proliferation, migration, invasion in vitro and tumor growth in vivo. Moreover, TRIM11 negatively regulated p53 expression. Knockdown of p53 abrogated the in vitro and in vivo biological functions of TRIM11 shRNA in HCC cells. CONCLUSIONS: These data show that TRIM11 exerts its oncogenic effect in HCC by downregulating p53 both in vitro and in vivo. Our data provide new insights into the pathogenesis of HCC and indicate that TRIM11 may serve as a new therapeutic target for HCC treatment.
Assuntos
Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Regulação para Cima , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Movimento Celular , Proliferação de Células , Ciclina D1/genética , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Regulação para Baixo , Transição Epitelial-Mesenquimal , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transplante Heterólogo , Proteínas com Motivo Tripartido/antagonistas & inibidores , Proteína Supressora de Tumor p53/antagonistas & inibidores , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína Ligases/antagonistas & inibidoresRESUMO
Divisive faultlines caused by the uneven distribution of relationship strength play an essential role in knowledge search in the technological innovation network, which serves as an important requirement for the technological innovation network's macro level to expand to the meso-subgroup level and promote its healthy development. Given that the biopharmaceutical industry, as a high-tech industry, plays a vital role in promoting healthy development, this paper uses the joint patent applications of global biopharmaceutical firms from 2003 to 2018 as a sample to construct a technological innovation network, to explore the relationship between divisive faultlines and knowledge search in the technological innovation network. We also study the moderating effect of structural holes in this relationship. The empirical results show that divisive faultlines significantly affect the depth of knowledge search in the technological innovation network. Divisive faultlines have an inverted U-shaped effect on the breadth of knowledge search in the technological innovation network. Structural holes positively moderate the relationship between divisive faultlines and depth of knowledge search but negatively moderate the inverted U-shaped relationship between divisive faultlines and breadth of knowledge search. This research reveals the relationship between divisive faultlines and the knowledge search in the technological innovation network. The research results provide a theoretical basis and management enlightenment to improve biopharmaceutical firms' knowledge search ability and promote healthy and sustainable development.
Assuntos
Produtos Biológicos , Invenções , Pesquisa Empírica , IndústriasRESUMO
The pressures to maintain a low-carbon economy makes green competitiveness (GC) a significant issue in China. It has been found that the development of Internet and E-commerce contributes significantly to GC of regional economy, yet there are still lack of quantitative investigation on their effects, which can be used to further guide the economic development. Therefore, this study constructs a new evaluation index for the green competitiveness of the regional manufacturing industry in China by introducing Internet application indicators and E-commerce development indexes into its evaluation system. The results show Jiangxi and Gansu moved upward significantly in the GC ranking over the period. The development of the Internet and E-commerce has the most significant impact on GC of regional manufacturing. The lack of green manufacturing capabilities and green innovation drivers led to a decline in the GC ranking of Liaoning, Tianjin, Guangxi and Heilongjiang. Finally, this study uses Moran's I index to investigate the spatial agglomeration effect of the green development of the manufacturing industry at the province level. The results show an increase in the GC of China's regional manufacturing industry, and the GC of manufacturing industry shows a significant agglomeration effect. Based on the above conclusions, the proposal to promote the balanced development of the GC of the manufacturing industry is proposed.