Background: The success of using glycolytic inhibitors for cancer treatment relies on better understanding the roles of each frequently deregulated glycolytic genes in cancer. This report analyzed the involvement of a key glycolytic enzyme, alpha-enolase (ENO1), in tumor progression and prognosis of human glioma.Methods: ENO1 expression levels were examined in glioma tissues and normal brain (NB) tissues. The molecular mechanisms of ENO1 expression and its effects on cell growth, migration and invasion were also explored by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, Transwell chamber assay, Boyden chamber assay, Western blot and in vivo tumorigenesis in nude mice.Results: ENO1 mRNA and protein levels were upregulated in glioma tissues compared to NB. In addition, increased ENO1 was associated disease progression in glioma samples. Knocking down ENO1 expression not only significantly decreased cell proliferation, but also markedly inhibited cell migration and invasion as well as in vivo tumorigenesis. Mechanistic analyses revealed that Cyclin D1, Cyclin E1, pRb, and NF-κB were downregulated after stable ENO1 knockdown in glioma U251 and U87 cells. Conversely, knockdown of ENO1 resulted in restoration of E-cadherin expression and suppression of mesenchymal cell markers, such as Vimentin, Snail, N-Cadherin, β-Catenin and Slug. Furthermore, ENO1 suppression inactivated PI3K/Akt pathway regulating the cell growth and epithelial-mesenchymal transition (EMT) progression.Conclusion: Overexpression of ENO1 is associated with glioma progression. Knockdown of ENO1 expression led to suppressed cell growth, migration and invasion progression by inactivating the PI3K/Akt pathway in glioma cells.

Glioblastoma has been identified as the most common and aggressive primary brain tumor in adults. Recently, it has been found that cisplatin (DDP) treatment is a common chemotherapeutic method for GBM patients. circ_PTN (ID number: hsa_circ_0003949) is a newly found circular (circRNA) which has been proved to be highly expressed in GBM cells, while its role in GBM remains unclear. Therefore, our study focused on investigating the role of circ_PTN in the DDP resistance of GBM cells. The expression of circ_PTN in DDP-sensitive and DDP-resistant GBM cells was detected in our assay. Functional experiments were utilized to unveil the effects of circ_PTN on the DDP resistance of GBM cells. Moreover, mechanism assays were conducted to confirm the mechanism of how circ_PTN affected the DDP resistance of GBM cells. According to the results, we found that circ_PTN promoted the DDP resistance of GBM cells through activation of the PI3K/AKT pathway. Moreover, circ_PTN silencing inhibited the DDP resistance of GBM tumors in vivo. To conclude, our study unveiled the influence of circ_PTN on the DDP resistance of GBM cells, which might provide a therapeutic target for GBM treatment via DDP.

The biological effect and molecular mechanism of miR‐5188 have not been thoroughly investigated. The study aims at elucidating the role of miR‐5188 in glioma progression. Human glioma cell lines and tissues were used for functional and expression analysis. Cellular and molecular techniques were performed to explore the functions and mechanisms of miR‐5188 in glioma. In our investigation, we demonstrated that miR‐5188 promoted cell proliferation, the G1/S transition of the cell cycle, migration and invasion in glioma and reduced the lifespan of glioma‐bearing mice. miR‐5188 directly targeted FOXO1 and activated PI3K/AKT‐c‐JUN signalling, which enhanced miR‐5188 expression. Moreover, the c‐JUN transcription factor functionally bound to the miR‐5188 promoter region, forming the positive feedback loop. The feedback loop promoted glioma progression through activating the PI3K/AKT signalling, and this loop is augmented by the interaction between SP1 and c‐JUN. Moreover, it was also found that the miR‐5188/FOXO1 axis is facilitated by SP1‐activated PI3K/AKT/c‐JUN signalling. In glioma samples, miR‐5188 expression was found to be an unfavourable factor and was positively associated with the mRNA levels of SP1 and c‐JUN, whereas negatively associated with the mRNA levels of FOXO1. Our investigation demonstrates that miR‐5188 could function as a tumour promoter by directly targeting FOXO1 and participating in SP1‐mediated promotion of cell growth and tumorigenesis in glioma.