ß 2 -Microglobulin Participates in the Development of Vestibular Schwannoma by Regulating Nuclear Factor-κB.

BACKGROUND AND OBJECTIVES: Vestibular schwannoma (VS), the most common intercranial schwannoma, originates from the sheath of the vestibular nerve. The growth rate of VS varies greatly, with the tumor enlarging gradually, which can compress the peripheral nerve tissue and reveal corresponding symptoms. This study was aimed to elucidate the growth mechanism of VS by analyzing cellular changes at protein, messenger ribonucleic acid (mRNA), and other molecular levels. METHODS: We determined mRNA and protein levels of ß 2 -microglobulin (ß 2 -M) and nuclear factor κB (NF-κB) in tumors of different sizes using the real-time polymerase chain reaction and Western blotting, respectively. The relationship between these factors was verified in VS primary cells cultured in vitro, and the potential role of ß 2 -M and NF-κB in VS growth was elucidated. RESULTS: In the secretions of freshly isolated tumor tissue cultured for 72 h, the concentration of ß 2 -M was positively correlated with the tumor diameter. Furthermore, tumors with larger diameter showed higher expressions of ß 2 -M and NF-κB at protein and mRNA level. ß 2 -M treatment resulted in elevated protein expression of NF-κB and also its phosphorylated form in vitro. CONCLUSION: ß 2 -M may participate in VS growth by regulating NF-κB and act as a key regulatory molecule in VS tumor growth.

The Role of MicroRNAs in Therapeutic Resistance of Malignant Primary Brain Tumors.

Brain tumors in children and adults are challenging tumors to treat. Malignant primary brain tumors (MPBTs) such as glioblastoma have very poor outcomes, emphasizing the need to better understand their pathogenesis. Developing novel strategies to slow down or even stop the growth of brain tumors remains one of the major clinical challenges. Modern treatment strategies for MPBTs are based on open surgery, chemotherapy, and radiation therapy. However, none of these treatments, alone or in combination, are considered effective in controlling tumor progression. MicroRNAs (miRNAs) are 18-22 nucleotide long endogenous non-coding RNAs that regulate gene expression at the post-transcriptional level by interacting with 3'-untranslated regions (3'-UTR) of mRNA-targets. It has been proven that miRNAs play a significant role in various biological processes, including the cell cycle, apoptosis, proliferation, differentiation, etc. Over the last decade, there has been an emergence of a large number of studies devoted to the role of miRNAs in the oncogenesis of brain tumors and the development of resistance to radio- and chemotherapy. Wherein, among the variety of molecules secreted by tumor cells into the external environment, extracellular vesicles (EVs) (exosomes and microvesicles) play a special role. Various elements were found in the EVs, including miRNAs, which can be transported as part of these EVs both between neighboring cells and between remotely located cells of different tissues using biological fluids. Some of these miRNAs in EVs can contribute to the development of resistance to radio- and chemotherapy in MPBTs, including multidrug resistance (MDR). This comprehensive review examines the role of miRNAs in the resistance of MPBTs (e.g., high-grade meningiomas, medulloblastoma (MB), pituitary adenomas (PAs) with aggressive behavior, and glioblastoma) to chemoradiotherapy and pharmacological treatment. It is believed that miRNAs are future therapeutic targets in MPBTs and such the role of miRNAs needs to be critically evaluated to focus on solving the problems of resistance to therapy this kind of human tumors.

Harmine suppresses bladder tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis.

Angiogenesis is a vital step during the process of oncogenesis of a lot of tumors, with no exception in bladder cancer. One of the useful strategies for the development of new drugs against cancer is targeting angiogenesis. In the present study, we found that a small-molecule natural product, which belonged to the ß-carboline alkaloid, named harmine, could strongly inhibit tumor angiogenesis thus exhibiting its ideal treatment efficacy in bladder cancer. In vivo study verified that harmine had the effect of inhibition on human bladder tumor xenograft growth. The inhibitory effect of harmine to bladder cancer growth was coordinated by the effects shown on angiogenesis. To further explore the pharmacological activities of harmine, we tested harmine's influence on blood vessel formation and found that harmine effectively blocked the microvessel sprouting in rat aortic ring assay when stimulated by vascular endothelial growth factor (VEGF). Furthermore, harmine inhibited human umbilical vein endothelial cell (HUVEC) proliferation as well as chemotactic motility, and when we treated HUVEC cell with harmine, the formation of capillary-like structures was also restrained. Moreover, harmine induced bladder cancer cell apoptosis through triggering the caspase-dependent apoptotic pathway and the downstream vascular endothelial growth factor receptor 2 (VEGFR2) kinase pathway was down-regulated, thus suppressing tumor development signals. Herein, our study demonstrated that natural product harmine might have potential in curing human bladder tumor because of its pharmacological function on tumor angiogenesis, trigged by VEGFR2 signaling pathways.