RESUMO
Esophageal squamous cell carcinoma (ESCC) is a tumor with high incidence and poor prognosis in developing countries. Junctional adhesion molecule A (JAM-A, also known as F11R) affects numerous biological processes, which is a vital regulator of the development of malignant tumors. However, its exact role and underlying mechanism in ESCC remain obscure. Our present study demonstrated that JAM-A was upregulated in ESCC tissues and cell lines by RNA sequencing and immunohistochemistry (IHC). JAM-A knockdown significantly suppressed the proliferation of the ESCC cells, induced cell cycle arrest at the G1 and promoted apoptosis, and suppressed the ability of invasion and migration in vivo and in vitro. Mechanistically, JAM-A may activate the NF-κB signaling pathway to regulate malignant behavior of ESCC. Further research showed that Homeobox D11 (HOXD11) could directly regulate JAM-A transcription by binding to specific sequences of JAM-A promoter region, thereby activating NF-κB signaling pathway to regulate malignant behavior of ESCC. Functional experiments indicated that HOXD11 could exert an oncogenic role in ESCC. Collectively, our findings support the hypothesis that the HOXD11/JAM-A/NF-κB signal axis plays a role in regulating malignant behavior in ESCC patients, highlighting its potential therapeutic value for ESCC.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Proteínas de Homeodomínio , NF-kappa B , Humanos , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , NF-kappa B/genética , NF-kappa B/metabolismo , Transdução de Sinais/genética , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismoRESUMO
OBJECTIVE: Exercise induced oscillatory ventilation (EIOB) during cardiopulmonary exercise testing (CPET) is associated with severity and prognosis of disease, but clinical approach for the character of EIOB due to circulatory dysfunction are seldom reported. METHODS: This retrospective analysis of symptom-limited maximum CPET data with an increment of 10-20 W/min in 38 patients with CHF. We calculated the duration, frequency, amplitude and other parameters of EIOB. RESULTS: There were 31 presenting with EIOB (82%) in all patients with CHF. In EIOB group, VE amplitude were (12.4 ± 4.4)L/min (accounting for 81% ± 30% of mean) and duration were (77.0 ± 20.0)s. The number of patients whose EIOB presenting at rest, exercise, recovery stage and the whole eriod were 24, 31, 4 and 4, respectively. Except VE, there were VO2, VCO2, RER and PETO2 presenting EIOB in all 31 patients; VE/VCO2, VO2/VE and breath frequency in 29 patients; PETCO2 in 26 patients; VT and VO2/HR in 25 patients; and HR in 2 patients. CONCLUSION: EIOB may occur in any period of CPET, mostly in severe patient with CHF, and presenting in many variables. Due to it is resulted from the circulatory dysfunction, we should call it circulatory (cardiac) oscillatory breathing abnormality.
