Background Accumulating evidence demonstrates the oncogenic roles of lncRNA (long non-coding RNA) molecules in a wide variety of cancer types including glioma. Equally important, However, tumorigenic functions of lncRNA in glioma remain largely unclear. A recent study suggested lncRNA SNHG15 played a role for regulating angiogenesis in glioma but its role in the tumor microenvironment (TME) was not investigated. Methods First, we showed that SNHG15 was upregulated in GBM cells and associated with a poor prognosis for the patients of GBM using public databases. Next, we collected temozolomide sensitive (TMZ-S) and resistant (TMZ-R) clinical samples and demonstrated that co-culturing TMZ-R cells with HMC3 (microglial) cells promoted M2-polarization of HMC3 and the secretion of pro-GBM cytokines TGF-β and IL-6. Results Comparative qPCR analysis of TMZ-S and TMZ-R cells showed that a significantly higher level of SNHG15, coincidental with a higher level of Sox2, β-catenin, EGFR, and CDK6 in TMZ-R cells. Subsequently, using bioinformatics tool, a potential mechanistic route for SNHG15 to promote GBM tumorigenesis was by inhibiting tumor suppressor, miR-627-5p which leads to activation of CDK6. Gene-silencing technique was employed to demonstrate that suppression of SNHG15 indeed led to the suppression of GBM tumorigenesis, accompanied by an increase miR-627-5p and decreased its two oncogenic targets, CDK6 and SOX-2. In addition, SNHG15-silenced TMZ-R cells became significantly sensitive towards TMZ treatment and less capable of promoting M2-phenotype in the HMC3 microglial cells. We then evaluated the potential anti-GBM activity of CDK6 inhibitor, palbociclib, using TMZ-R PDX mouse models. Palbociclib treatment significantly reduced tumorigenesis in TMZ-R/HMC3 bearing mice and SNHG15 and CDK6 expression was significantly reduced while miR-627-5p level was increased. Additionally, palbociclib treatment appeared to overcome TMZ resistance as well as reduced M2 markers in HMC3 cells. Conclusion Together, we provided evidence supporting the usage of CDK6 inhibitor for TMZ-resistant GBM cases. Further investigation is warranted for the consideration of clinical trials. Graphical abstract Electronic supplementary material The online version of this article (10.1186/s13046-019-1371-0) contains supplementary material, which is available to authorized users.

Human fetal neural stem cells (hNSCs) are used to treat a variety of neurological disorders involving spinal cord injury (SCI). Although their mechanism of action has been attributed to cell substitution, we examined the possibility that NSCs may have neuroprotective activities. The present article studied the action of hNSCs on protecting neurons and promoting corticospinal tract (CST) axon regeneration after SCI. hNSCs were isolated from the cortical tissue of spontaneously aborted human fetuses. The cells were removed from the NSC culture medium to acquire NSCM, thus excluding the effect of cell substitution. Continuous administration of the NSCM after the SCI resulted in extensive growth of the CST in the cervical region and more than tripled the formation of synaptic contacts between CST collaterals and propriospinal interneurons that project from the cervical level of the spinal cord to the lumbar level. NSCM reduced the number of caspase 3-positive apoptotic profiles at 7 days and protected against loss of the neurons 6 weeks after injury. NSCM promoted locomotor recovery with a five-point improvement on the BBB scale in adult rats. Thus, hNSCs help to set up a contour neural circuit via secretory factors, which may be the mechanism for their action in SCI rats. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

Accumulating evidence indicates long noncoding RNAs (lncRNA) play a vital role in tumor progression. However, the role of linc00645-induced accelerated malignant behavior in glioblastoma (GBM) remains unknown. In the present study, linc00645 expression was significantly upregulated in GBM tissues and cell lines. High level of linc00645 was associated with poor overall survival in GBM patients. Knockdown of linc00645 suppressed the proliferation, stemness, migration, invasion, and reversed transforming growth factor (TGF)-β-induced motility of glioma cell lines. Furthermore, linc00645 directly interacted with miR-205-3p and upregulated of miR-205-3p impeded efficiently the increase of ZEB1 induced by linc00645 overexpression. Moreover, knockdown of linc00645 significantly suppressed the progression of glioma cells in vivo. miR-205-3p was a target of linc00645 and linc00645 modulates TGF-β-induced glioma cell migration and invasion via miR-205-3p. Taken together, our findings identified the linc00645/miR-205-3p/ZEB1 signaling axis as a key player in EMT of glioma cells triggered by TGF-β. These data elucidated that linc00645 plays an oncogenic role in glioma and it may serve as a prognostic biomarker and a potential therapeutic target for the treatment of glioma in humans.

No abstract

The aim of this study was to research the mechanism of circMAN2B2 in the development of glioma. In our study, we found that circMAN2B2 has a higher expression in glioma tissues and cells, which was negatively related to the overall survival of glioma patients. The cell counting kit-8 assay, 5-ethynyl-2′-deoxyuridine labeling assay, transwell assay, and the nude mice assay indicated that knockdown of circMAN2B2 inhibited the cell proliferation, invasion, migration and decreased tumor size. In terms of mechanism, knockdown of circMAN2B2 increased the expression of miR-1205. Moreover, circMAN2B2 regulated S100A8 expression by inhibiting miR-1205. We also showed that knockdown of S100A8 inhibited cell proliferation, invasion, and migration. Increasing S100A8 expression rescued the effect of si-circMAN2B2. In conclusion, circMAN2B2 could improve cell proliferation, invasion, and migration of the glioma by inhibiting miR-1205 and promoting the expression of S100A8. K E Y W O R D ScircMAN2B2, glioma, miR-1205, S100A8