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Neurons are post‐mitotic cells, with microtubules playing crucial roles in axonal transport and growth. Kinesin family member 2c (KIF2C), a member of the Kinesin‐13 family, possesses the ability to depolymerize microtubules and is involved in remodelling the microtubule lattice. Myocyte enhancer factor 2c (MEF2C) was initially identified as a regulator of muscle differentiation but has recently been associated with neurological abnormalities such as severe cognitive impairment, stereotyping, epilepsy and brain malformations when mutated or deleted. However, further investigation is required to determine which target genes MEF2C acts upon to influence neuronal function as a transcription regulator. Our data demonstrate that knockdown of both Mef2c and Kif2c significantly impacts spinal motor neuron development and behaviour in zebrafish. Luciferase reporter assays and chromosome immunoprecipitation assays, along with down/upregulated expression analysis, revealed that MFE2C functions as a novel transcription regulator for the Kif2c gene. Additionally, the knockdown of either Mef2c or Kif2c expression in E18 cortical neurons substantially reduces the number of primary neurites and axonal branches during neuronal development in vitro without affecting neurite length. Finally, depletion of Kif2c eliminated the effects of overexpression of Mef2c on the neurite branching. Based on these findings, we provided novel evidence demonstrating that MEF2C regulates the transcription of the Kif2c gene thereby influencing the axonal branching. [ABSTRACT FROM AUTHOR]

Although much progress has been made in the treatment of gliomas, the prognosis for patients with gliomas is still very poor. Stem cell‐based therapies may be promising options for glioma treatment. Recently, many studies have reported that umbilical cord‐derived mesenchymal stromal/stem cells (UC‐MSCs) are ideal gene vehicles for tumor gene therapy. Interleukin 24 (IL‐24) is a pleiotropic immunoregulatory cytokine that has an apoptotic effect on many kinds of tumor cells and can inhibit the growth of tumors specifically without damaging normal cells. In this study, we investigated UC‐MSCs as a vehicle for the targeted delivery of IL‐24 to tumor sites. UC‐MSCs were transduced with lentiviral vectors carrying green fluorescent protein (GFP) or IL‐24 complementary DNA. The results indicated that UC‐MSCs could selectively migrate to glioma cells in vitro and in vivo. Injection of IL‐24‐UC‐MSCs significantly suppressed tumor growth of glioma xenografts. The restrictive efficacy of IL‐24‐UC‐MSCs was associated with the inhibition of proliferation as well as the induction of apoptosis in tumor cells. These findings indicate that UC‐MSC‐based IL‐24 gene therapy may be able to suppress the growth of glioma xenografts, thereby suggesting possible future therapeutic use in the treatment of gliomas. [ABSTRACT FROM AUTHOR]

Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins and has been proved to contribute to the migration of a variety of solid tumor cells. However, whether DSPP participates in the pathogenic process of glioma remains unknown. In this study, we aimed to investigate the expression and biological function of DSPP in human glioma cells. We demonstrated through Western blot that DSPP is overexpressed in glioma tissues comparing to normal brain tissues. To investigate the role of DSPP in glioma carcinogenesis, we reduced the DSPP expression by small interfering RNA (siRNA) and found that DSPP silencing significantly inhibited the migration and invasion of glioma cells, the critical characteristics of glioma. Furthermore, we showed that DSPP down-regulation significantly decreased the activation of the AKT/mTOR/p70S6K pathway in glioma cells. Taken together, these findings indicate that knockdown of DSPP inhibits glioma cells migration and invasion, suggesting that targeting DSPP might be a potentially effective therapeutic strategy for treating glioma., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Objective: To investigate the effects of BCNU/PLGA microspheres on tumor growth, apoptosis and chemotherapy resistance in a C57BL/6 mice orthotopic brain glioma model using GL261 cell line., Methods: BCNU/PLGA sustained-release microspheres were prepared by the water-in-oil-in-water emulsion technique. GL261 cells were intracranially injected into C57BL/6 mouse by using the stereotactic technology. A total of 60 tumor-bearing mice were randomly and equally divided into three groups: untreated control, PLGA treated, BCNU/PLGA treated. Magnetic resonance imaging (MRI) was taken to evaluate tumor volume. BCNU/PLGA sustained-release wafers were implanted in the treatment group two weeks after inoculation. Survival time and quality were observed. Specimens were harvested, and immunohistochemical staining was used to check the expression of Bax, Bcl-2, and O(6)-methylguanine-DNA methyltransferase (MGMT). Statistical methods was used for analysis of relevant data., Results: BCNU/PLGA sustained-release wafers were fabricated and implanted successfully. There is statistical difference of survival time between the BCNU/PLGA treated group and control groups (P<0.05). MRI scan showed inhibitory effect of BCNU/PLGA on tumor growth. Compared to the group A and B, BCNU/PLGA decreased the expression of apoptosis related gene Bcl-2 (P<0.05), but did not elevate the expression level of Bax (P>0.05), with the ratio of Bax/Bcl-2 increased. For MGMT protein expression, no statistically significant change was found in treated group (P>0.05)., Conclusions: Local implantation of BCNU/PLGA microspheres improved the survival quality and time of GL261 glioma-bearing mice significantly, inhibited the tumor proliferation, induced more cell apoptosis, and did not increase the chemotherapy resistance.