RESUMO
Competing endogenous RNAs (ceRNAs) represent a novel layer regulations of long non-coding RNAs (lncRNAs) and genes that play important roles in cancer pathogenesis by binding microRNAs (miRNAs). However, the competition mechanism of ceRNAs in cholangiocarcinoma (CHOL) is not fully understood. In this study, we constructed a dysregulated ceRNA competitive network (CCEN) to globally characterize the competing difference between CHOL and normal tissues. Then, we integrated affinity propagation and KaplanMeier (K-M) methods to identify functional clusters associated with survival. A total of 7 key ceRNA clusters were identified. Further functional annotation analyses found that Cluster23 and Cluster32 involved cell based functions, and the loss of ceRNA competitive relations in clusters may contribute to CHOL, by disturbing important biological processes, such as 'Pathway in cancer', MAPK and Neurotrophin signaling pathway. This study provides further insights into understanding the competitive mechanism of ceRNAs in CHOL.
Assuntos
Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/genética , Redes Reguladoras de Genes/genética , RNA Longo não Codificante/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Família MultigênicaRESUMO
Interleukin-6 (IL-6), through activation of the signal transducer and activator of transcription 3 (STAT3) and trefoil factor family 3 (TFF3), has been implicated in the promotion of mouse biliary epithelial cell (BEC) proliferation and migration. However, it is still unclear whether the IL-6/STAT3/TFF3 signaling had similar effects on human BECs. Here, we showed that exposure of human BECs to recombinant IL-6 resulted in STAT3 phosphorylation and increased the expression of TFF3 at both mRNA and protein levels. Moreover, inhibition of STAT3 using RNA interference significantly abrogated IL-6-induced TFF3 expression. In an in-vitro wound healing model, IL-6 facilitated human BEC migration. This promotion of cell migration by IL-6 was blocked when STAT3 was knocked down. Interestingly, the addition of exogenous TFF3 could rescue the cell migration defects caused by STAT3 silencing. In conclusion, our data indicate that STAT3 plays a critical role in IL-6-induced TFF3 expression in human BECs and the IL-6/STAT3/TFF3 signaling is involved in human BEC migration and wound healing.
Assuntos
Movimento Celular , Células Epiteliais/patologia , Interleucina-6/metabolismo , Peptídeos/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Cicatrização , Animais , Sistema Biliar/patologia , Bioensaio , Células Epiteliais/metabolismo , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Peptídeos/genética , Fosforilação , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator Trefoil-3RESUMO
Optical coherence tomography is an appropriate imaging method for biomedical science, due to its advantages of noninvasive nature, high resolution and fast imaging speed. Because most biological tissues have the characteristic of high scattering coefficient, OCT system can just obtain the structural images several millimeters below the surface of the tissues. The superficial depth of OCT's penetration limits application in dermatology field. As a common disease, the port wine stain (PWS) is a indication of OCT, because of its superficial lesion and significant expansion of blood vessels. To get deeper penetration in the skin, the authors employed 1 310 nm superluminescent diode as light source, optimized the light intensity ratio of reference delay arm and sample arm and control polarization, and the research of PWS imaging in vivo was accomplished. Besides, OCT is able to gather clear image and key characteristic parameters, such as the depth of epidermis layer, the diameter of blood vessel, etc. OCT will play an important role in the diagnosis and therapy of PWS.
Assuntos
Mancha Vinho do Porto , Tomografia de Coerência Óptica , Humanos , Luz , PeleRESUMO
BACKGROUND: Secreted Frizzled-related protein 1 (sFRP1) is frequently silenced in many types of cancer, including hepatocellular carcinoma (HCC), leading to aberrant activation of Wnt signaling and thereby facilitating tumor development. In this study, we aimed to investigate whether restoration of sFRP1 affected HCC growth and metastasis. METHODS: We generated stable cell lines overexpressing sFRP1 in MHCC97-H cells, which naturally do not express detectable sFRP1 messenger RNA (mRNA) and have high metastatic properties. The effects of sFRP1 reexpression on tumor growth and metastasis were assessed in vitro and in vivo. It was also tested whether ß-catenin signaling mediated the function of sFRP1 in tumor progression. RESULTS: Overexpression of sFRP1 substantially diminished the proliferation and invasion potentials of MHCC97-H cells. Furthermore, sFRP1 expression significantly inhibited MHCC97-H xenograft growth and metastasis in vivo, which was accompanied by decreased angiogenesis and increased tumor cell apoptosis. Moreover, sFRP1 overexpression caused less expression of ß-catenin and its downstream effector genes cyclin D1 and matrix metalloproteinase (MMP)-2. CONCLUSION: Together these findings demonstrate that sFRP1 reconstitution suppresses tumor growth, angiogenesis, and metastasis in MHCC97-H xenografts, which may be associated with inactivation of ß-catenin signaling, thus providing a possible therapeutic strategy against HCC.