RESUMO
Hepatitis B virus (HBV) and one of its encoded proteins, HBV X protein (HBx), have been shown to induce autophagy in hepatoma cells. Substantial evidence indicates that autophagy is a potent suppressor of inflammation. However, sporadic reports suggest that autophagy could promote pro-inflammatory cytokine expression and inflammation in some biological contexts. Here, we show that overexpression of HBx induces LC3B-positive autophagosome formation, increases autophagic flux and enhances the expression of ATG5, ATG7, and LC3B-II in normal hepatocytes. Abrogation of autophagy by small interfering RNA against ATG5 and ATG7 prevents HBx-induced formation of autophagosomes. Autophagy inhibition also abrogates HBx-induced activation of nuclear factor-κB (NF-κB) and production of interleukin-6 (IL-6), IL-8, and CXCL2. These findings suggest that autophagy is required for HBx-induced NF-κB activation and pro-inflammatory cytokine production and could shed new light on the complex role of autophagy in the modulation of inflammation.
Assuntos
Autofagia/fisiologia , Quimiocina CXCL2/metabolismo , Vírus da Hepatite B/isolamento & purificação , Hepatócitos/metabolismo , Interleucina-6/biossíntese , Interleucina-8/biossíntese , NF-kappa B/metabolismo , Linhagem Celular , Regulação da Expressão Gênica/fisiologia , Humanos , Neoplasias Hepáticas/metabolismo , Transdução de Sinais/fisiologia , Transativadores/metabolismo , Proteínas Virais Reguladoras e AcessóriasRESUMO
Nasopharyngeal carcinoma (NPC) is a highly malignant cancer with local invasion and early distant metastasis. NPC is highly prevalent in the Southern China and South-eastern Asia. The genetic susceptibility, endemic environment factors, and Epstein-Barr virus (EBV) infection are believed to be the major etiologic factors of NPC. Once metastasis occurs, the prognosis is very poor. It is urgently needed to develop biomarkers for early clinical diagnosis/prognosis, and novel effective therapies for nasopharyngeal carcinoma. In this paper, we systematically reviewed the current progress of miRNA studies in NPC. It has been shown that both host encoded miRNAs and EBV encoded miRNAs play key roles in almost all the steps of epithelia cell carcinogenesis, including epithelial-mesenchymal to stem-like transition, cell growth, migration, invasion, and tumorigenesis. More importantly, some miRNAs could be secreted out and play a role in the microenvironments. The level of sera miRNAs is correlated with the copy numbers of host miRNAs in tumor biopsies. Promising results of gene therapy have been also achieved by lentiviral delivered miRNAs. Taken together, cell free miRNAs would be potential biomarkers of early clinical diagnosis/prognosis; while some miRNAs could be further developed into therapeutic agents in the future.
Assuntos
Herpesvirus Humano 4 , MicroRNAs/análise , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/virologia , Biomarcadores Tumorais/análise , Carcinoma , Terapia Genética/métodos , Herpesvirus Humano 4/genética , Humanos , Terapia de Alvo Molecular , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/terapia , Prognóstico , RNA Viral/análiseRESUMO
Multiple intracellular signaling pathways, such as Wnt/ß-catenin signaling, epidermal growth factor receptor/Ras signaling, and p53 signaling are frequently dysregulated in colorectal cancer. Recent evidence also points to the involvement of signaling pathways in the developmental process, including Notch signaling, Hedgehog signaling, and Hippo signaling. Dysregulation of these signaling pathways contribute to the acquisition of malignant phenotypes, including unchecked cell cycle progression, evasion of apoptosis, induction of genetic instability, and enhanced invasiveness and metastasis. Understanding their relative importance and crosstalk will provide a rational basis for anticancer drug development.