miR-23b/SP1/c-myc forms a feed-forward loop supporting multiple myeloma cell growth

Deregulated microRNA (miR)/transcription factor (TF)-based networks represent a hallmark of cancer. We report here a novel c-Myc/miR-23b/Sp1 feed-forward loop with a critical role in multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM) cell growth and survival. We have found miR-23b to be downregulated in MM and WM cells especially in the presence of components of the tumor bone marrow milieu. Promoter methylation is one mechanism of miR-23b suppression in myeloma. In gain-of-function studies using miR-23b mimics-transfected or in miR-23b-stably expressing MM and WM cell lines, we observed a significant decrease in cell proliferation and survival, along with induction of caspase-3/7 activity over time, thus supporting a tumor suppressor role for miR-23b. At the molecular level, miR-23b targeted Sp1 3'UTR and significantly reduced Sp1-driven nuclear factor-kappa B activity. Finally, c-Myc, an important oncogenic transcription factor known to stimulate MM cell proliferation, transcriptionally repressed miR-23b. Thus MYC-dependent miR-23b repression in myeloma cells may promote activation of oncogenic Sp1-mediated signaling, representing the first feed-forward loop with critical growth and survival role in myeloma

Financial distress prediction based on SVM and MDA methods: the case of Chinese listed companies

Financial distress prediction, Support vector machine, Multivariate discriminant analysis, Financial variables, Non-financial variables,

Russell and Rubinstein's Pathology of Tumors of the Nervous System. Sixth Edition

An increasing number of parasites are being added to the list of those that can be transmitted via food or water and that pose a risk to human health if ingested. These zoonotic infections usually have complicated life cycles requiring a number of hosts for completion or a diversity of cycles of transmission that may interact. The challenge in all control efforts is to break the cycle of transmission that may lead to human infection, which requires the ability to detect and characterize the relevant parasite life cycle stage in food or water. This requires tools that are both sensitive and specific, and often beyond the limitations of conventional techniques such as microscopy