RESUMO
While estrogen receptor ß (ERß) may impact the progression of non-small cell lung cancer (NSCLC), its linkage to alteration of the vasculogenic mimicry (VM) formation to influence the NSCLC cell invasion remains unclear. Here, we analyzed immunohistochemistry data from NSCLC tissues and found that ERß-positive NSCLC female patients had worse survival outcomes than those of ERß-negative NSCLC female patients. In vitro studies using multiple NSCLC cell lines also revealed that ERß could increase the VM formation and cell invasion. Molecular mechanism dissection suggested that ERß could increase the lncRNA-MALAT1 (MALAT1) expression via directly binding to the estrogen response elements (EREs) located on the promoter of MALAT1, which could then lead to (i) suppressing the miR145-5p and (ii) increasing the NEDD9 protein expression as miR145-5p can directly target the 3'-UTR of NEDD9-mRNA. A preclinical study using the in vivo mouse model further confirmed the in vitro cell lines data. Together, results from the above studies demonstrated that ERß can promote NSCLC VM formation and cell invasion via altering the ERß/MALAT1/miR145-5p/NEDD9 signaling. Targeting this newly identified signaling pathway with small molecules may help the development of novel therapies to better suppress the NSCLC metastasis.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Receptor beta de Estrogênio/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Fosfoproteínas/genética , RNA Longo não Codificante/genética , Animais , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Transdução de SinaisRESUMO
The Epstein-Barr virus (EBV) is a common virus in humans and the most common causative agent of Infectious Mononucleosis. EBV primary infection has recently risen in some countries and children below 2 years of age are highly susceptible. The clinical manifestations in children with EB virus infection involve multiple systems, causing severe illness, meaning attention should be paid during diagnosis and treatment. Objective: This single institution based retrospective study was carried out with the aim of estimating the overall prevalence of EBV infection and identifying high-risk age group among children. Methods: This study include total 253 patients under 15 years of age found to be positive for EBV DNA by PCR who were admitted to the Pediatrics Department of Renmin Hospital,(Shiyan, China) during a 4-year period from 2014 to 2017. Patients were divided into three groups; 0-<4years, 4-<6years and 6-<15years. We then calculated the percentage and prevalence of EBV DNA-positive cases. Results: The yearly EBV prevalence rate was 4.99 per 1000 admissions in 2014, 6.97 per 1000 admissions in 2015, 10.42 per 1000 admissions in 2016, and 12.16 per 1000 admissions in 2017. Out of 253 EBV-positive cases, those under 4 years had the highest rate of EBV infection (74.7%). The rate drops to 11.06% in the 4-6 years group, and was 14.22% in the 6-15 years group. Those between 6 months and 1 year are those at the highest risk. Conclusion: The rate of hospital admission of children due to EBV infection is increasing day by day. Children under 4 years of age are highly susceptible to infection and children of age between 6 months and 1 year are the high-risk group for EBV infection.