Research Progress on the Regulation Mechanism of Key Signal Pathways Affecting the Prognosis of Glioma

Abstract

As is known to all, glioma, a global difficult problem, has a high malignant degree, high recurrence rate and poor prognosis. We analyzed and summarized signal pathway of the Hippo/YAP, PI3K/AKT/mTOR, miRNA, WNT/β-catenin, Notch, Hedgehog, TGF-β, TCS/mTORC1 signal pathway, JAK/STAT signal pathway, MAPK signaling pathway, the relationship between BBB and signal pathways and the mechanism of key enzymes in glioma. It is concluded that Yap1 inhibitor may become an effective target for the treatment of glioma in the near future through efforts of generation after generation. Inhibiting PI3K/Akt/mTOR, Shh, Wnt/β-Catenin, and HIF-1α can reduce the migration ability and drug resistance of tumor cells to improve the prognosis of glioma. The analysis shows that Notch1 and Sox2 have a positive feedback regulation mechanism, and Notch4 predicts the malignant degree of glioma. In this way, notch cannot only be treated for glioma stem cells in clinic, but also be used as an evaluation index to evaluate the prognosis, and provide an exploratory attempt for the direction of glioma treatment. MiRNA plays an important role in diagnosis, and in the treatment of glioma, VPS25, KCNQ1OT1, KB-1460A1.5, and CKAP4 are promising prognostic indicators and a potential therapeutic targets for glioma, meanwhile, Rheb is also a potent activator of Signaling cross-talk etc. It is believed that these studies will help us to have a deeper understanding of glioma, so that we will find new and better treatment schemes to gradually conquer the problem of glioma.

CKAP4-mediated activation of FOXM1 via phosphorylation pathways regulates malignant behavior of glioblastoma cells

“…Considering that the decreased FOXM1 expression is rescued by the restoration of CKAP4 expression, we determined the regulatory effect of CKAP4 on FOXM1 expression [29] , followed by illustrating its carcinogenesis in GBM. As was the case in previous studies [49] , [50] , [51] , this study also detected an elevated expression of FOXM1 and CKAP4 in GBMs when compared to normal tissues. Our data displayed that CKAP4 activated FOXM1 expression at the post-transcriptional level.…”

ODF3B affects the proliferation and apoptosis of glioma via the JAK/STAT pathway

“…Enrichment of the KEGG pathway showed that ODF3B was associated with herpes simplex virus type 1 infection, Epstein-Barr virus infection, human immunodeficiency virus type 1 infection, the YAK-STAT signaling pathway, tolllike receptor signaling pathway, etc. The JAK/ STAT pathway is involved in biological processes such as growth, apoptosis, differentiation, and immune regulation of glioma cells [29][30][31]. Therefore, we speculated that ODF3B can affect the proliferation and apoptosis of gliomas through the JAK/STAT pathway.…”

The Spectrum of Molecular Pathways in Gliomas—An Up-to-Date Review

“…An important example is the investigation of activators of the JAK/Stat pathway such as Runx1 and VPS25, which are overexpressed in glioma tissues and thus serve as potential therapeutic targets [ 38 , 39 ]. Currently, research on the NOTCH pathway is particularly challenging, as its downregulation may have negative effects on gliomas by impairing tumor growth but also tumor-promoting effects by promoting angiogenesis [ 36 , 42 , 43 ]. The role of the WNT pathway is also becoming increasingly important in glioma research, and evidence for its involvement in glioma growth is the tumor-promoting effect of the RNA-binding protein FMRP, which is overexpressed in glioblastomas.…”

“…Its central protein families are the Janus kinases (JAKs) and the signal transducers and activators of transcription proteins (STATs), which are a signal transduction pathway from the cell membrane to the nucleus due to activation by growth factors and cytokines, such as interleukins and interferons. In general, JAKs are activated by the binding of ligands, leading to the phosphorylation and activation of STATs, which migrate to the nucleus and interact with specific DNA-binding sites [ 36 , 37 ]. Different proteins of the JAK and STAT family are involved in different tasks such as immunomodulation, transcription, and tumorigenesis.…”

“…This signaling pathway is unique to gliomas for two reasons: First, it is not a pathway of soluble molecules, but a cell-to-cell interaction with transmembrane ligands that bind and activate a transmembrane receptor of a neighboring cell. Secondly, NOTCH signaling is a double-edged sword when it comes to exploiting this pathway for therapeutic options, as its down-regulation has implications for reduced tumor growth, but on the other hand, reduced NOTCH signaling may promote aberrant tumor vessel formation and thus promote tumor growth [ 36 , 42 , 43 ]. There is a need for further clarification here, and the question even arises as to whether targeting NOTCH signaling has different effects at different stages of tumor progression [ 42 ].…”