BackgroundMicroRNA-381 (miR-381) has been reported to play suppressive or promoting roles in different malignancies. However, the expression level, biological function, and underlying mechanisms of miR-381 in gastric cancer remain poorly understood. Our previous study indicated that transmembrane protein 16A (TMEM16A) contributed to migration and invasion of gastric cancer and predicted poor prognosis. In this study, we found that miR-381 inhibited the metastasis of gastric cancer through targeting TMEM16A expression.MethodsMiR-381 expression was analyzed using bioinformatic software on open microarray datasets from the Gene Expression Omnibus (GEO) and confirmed by quantitative RT-PCR (qRT-PCR) in human gastric cancer tissues and cell lines. Cell proliferation was investigated using MTT and cell count assays, and cell migration and invasion abilities were evaluated by transwell assay. Xenograft nude mouse models were used to observe tumor growth and pulmonary metastasis. Luciferase reporter assay, western blot, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were employed to explore the mechanisms of the effect of miR-381 on gastric cancer cells.ResultsMiR-381 was significantly down-regulated in gastric cancer tissues and cell lines. Low expression of miR-381 was negatively related to lymph node metastasis, advanced tumor stage and poor prognosis. MiR-381 decreased gastric cancer cell proliferation, migration and invasion in vitro and in vivo. TMEM16A was identified as a direct target of miR-381 and the expression of miR-381 was inversely correlated with TMEM16A expression in gastric cancer tissues. Combination analysis of miR-381 and TMEM16A revealed the improved prognostic accuracy for gastric cancer patients. Moreover, miR-381 inhibited TGF-β signaling pathway and down-regulated epithelial–mesenchymal transition (EMT) phenotype partially by mediating TMEM16A.ConclusionsMiR-381 may function as a tumor suppressor by directly targeting TMEM16A and regulating TGF-β pathway and EMT process in the development of progression of gastric cancer. MiR-381/TMEM16A may be a novel therapeutic candidate target in gastric cancer treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0499-z) contains supplementary material, which is available to authorized users.
Therapeutic development is critical for preventing and treating continual MERS-CoV infections in humans and camels. Because of their small size, nanobodies (Nbs) have advantages as antiviral therapeutics (e.g., high expression yield and robustness for storage and transportation) and also potential limitations (e.g., low antigen-binding affinity and fast renal clearance). Here, we have developed novel Nbs that specifically target the receptor-binding domain (RBD) of MERS-CoV spike protein. They bind to a conserved site on MERS-CoV RBD with high affinity, blocking RBD's binding to MERS-CoV receptor. Through engineering a C-terminal human Fc tag, the in vivo half-life of the Nbs is significantly extended. Moreover, the Nbs can potently cross-neutralize the infections of diverse MERS-CoV strains isolated from humans and camels. The Fc-tagged Nb also completely protects humanized mice from lethal MERS-CoV challenge. Taken together, our study has discovered novel Nbs that hold promise as potent, cost-effective, and broad-spectrum anti-MERS-CoV therapeutic agents.
The metabolic switch from oxidative phosphorylation to glycolysis is required for tumorigenesis in order to provide cancer cells with energy and substrates of biosynthesis. Therefore, it is important to elucidate mechanisms controlling the cancer metabolic switch. MTR4 is a RNA helicase associated with a nuclear exosome that plays key roles in RNA processing and surveillance. We demonstrate that MTR4 is frequently overexpressed in hepatocellular carcinoma (HCC) and is an independent diagnostic marker predicting the poor prognosis of HCC patients. MTR4 drives cancer metabolism by ensuring correct alternative splicing of pre-mRNAs of critical glycolytic genes such as GLUT1 and PKM2. c-Myc binds to the promoter of the MTR4 gene and is important for MTR4 expression in HCC cells, indicating that MTR4 is a mediator of the functions of c-Myc in cancer metabolism. These findings reveal important roles of MTR4 in the cancer metabolic switch and present MTR4 as a promising therapeutic target for treating HCC.
BackgroundIntracranial vestibular schwannoma still remain to be difficulty for its unique microsurgical technique and preservation of neuro-function, as well as reducing common complications that may arise in surgery.MethodsWe consecutively enrolled 657 unilateral giant (>4 cm diameter) vestibular schwannoma patients treated in Huashan Hospital via the suboccipital retrosigmoid approach in the past 16 years. The extension of tumor removal, surgical mortality, facial nerve function, hearing, and the other main short and long-term complications were the studied parameters.ResultsGross total resection was performed in 556 patients (84.6%); near-total resection was achieved in 99 patients (15.1%). The mortality rate is 0.6%. The main short-term complications included ‘new’ deafness (47.6%), intracranial infection (7.6%), lower cranial nerve defects (7.5%) and pneumonia (6.2%). The facial nerve was preserved anatomically in 589 cases (89.7%). Good facial nerve functional outcome (House-Brackmann Grades I and II) postoperatively was achieved in 216 patients (32.9%). Other 308 cases (46.9%) were House-Brackmann grade III, and 133 patients (20.2%) were House-Brackmann grade IV–VI. Follow-up data were available for 566 of the 657 patients (86.1%). The common long-term complications were hearing loss (85.2%), facial paralysis (HB grade IV–VI, 24.4%) and facial numbness (15.7%).ConclusionsTrends in the data lead the authors to suggest that the microsurgical technique, intraoperative nerve monitoring, and multidisciplinary cooperation, were the keys to improving prognostic outcomes in giant intracranial vestibular schwannoma patients.
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