CircRNA circHIPK3 serves as a prognostic marker to promote glioma progression by regulating miR-654/IGF2BP3 signaling.

Emerging evidences show RNA back-splicing produces a new type of noncoding RNA, namely circular RNA (circRNA). Many reports demonstrate that circRNA circHIPK3 exerts oncogenic or anti-tumor roles in different cancers, such as ovarian cancer, bladder cancer, osteosarcoma, colorectal cancer and liver cancer. However, no study about circHIPK3 function in glioma exists until today. In this study, we showed that circHIPK3 was upregulated in glioma tissues. Elevated level of circHIPK3 was linked to poor prognosis. Functional investigation indicated that circHIPK3 promotes glioma cell proliferation and invasion, and tumor propagation in vivo. Furthermore, miR-654 was identified as a target of circHIPK3 while IGF2BP3 was targeted by miR-654. CircHIPK3 could promote IGF2BP3 expression via interacting with miR-654 in glioma cells. Finally, CCK8 and transwell assays illustrated that IGF2BP3 overexpression could reverse the effects of IGF2BP3 depletion. Altogether, our findings demonstrated that circHIPK3 contributes to glioma progression through targeting miR-654 from IGF2BP3 and implies circHIPK3 might be a potential target for glioma therapy.

Notch1 Signaling Activation Contributes to Adult Hippocampal Neurogenesis Following Traumatic Brain Injury.

BACKGROUND Neural stem cells are reported to exist in the hippocampus of adult mammals and are important sources of neurons for repair. The Notch1 signaling pathway is considered as one of the important regulators of neural stem cells, but its role in adult brains is unclear. We aimed to describe the role of Notch1 signaling in the adult rat hippocampus after traumatic brain injury. MATERIAL AND METHODS The model rats were randomly divided into 4 groups as follows: sham, sham-TBI, sham-Ad-TBI, and NICD-Ad-TBI. We used adenovirus-mediated gene transfection to upregulate endogenous NICD in vivo. Firstly, a TBI rat model was constructed with lateral fluid percussion. Then, the hippocampus was collected to detect the expression of Notch1 markers and stem cell markers (DCX) by Western blot analysis, immunohistochemistry, and immunofluorescence. The prognosis after TBI treatment was evaluated by the Morris Water Maze test. RESULTS First, we found the expression of NICD in vivo was significantly increased by adenovirus-mediated gene transfection as assessed by Notch1 immunofluorescence and Western blot analysis. Second, enhancing NICD stimulated the regeneration of neural stem cells in the DG of the adult rat brain following traumatic brain injury, as evaluated by DCX and NeuN double-staining. Furthermore, Notch1 signaling activation can promote behavioral improvement after traumatic brain injury, including spatial learning and memory capacity. CONCLUSIONS Our findings suggest that targeted regulation of Notch1 signaling may have a useful effect on stem cell transformation. Notch1 signaling may have a potential brain-protection effect, which may result from neurogenesis.

IL-13 receptor α2 stimulates human glioma cell growth and metastasis through the Src/PI3K/Akt/mTOR signaling pathway.

Glioma is a malignant tumor that affects all kinds of people all over the world. It demonstrates remarkable infiltrative and invasive features. The high expression of interleukin-13 receptor subunit alpha-2 (IL-13Rα2) reportedly plays a pivotal role in some cancers. However, whether IL-13Rα2 contributes to glioma remains unknown. This study demonstrates that IL-13Rα2 is significantly up-regulated in human glioma tissue samples. It is also associated with late stages of disease progression and diminished survival in glioma patients. Gain- and loss-of-function studies demonstrate that IL-13Rα2 promotes the growth, migration, and invasion of glioma cells. In addition, mechanistic investigations show that IL-13Rα2 activates Scr, phosphatidylinositol 3 kinase (PI3K), Akt, and mTOR. Also, restraining Scr in glioma cells attenuates the activation of Scr/PI3K/Akt/mTOR pathway by IL-13Rα2, whereas the silencing of Scr markedly rescues the pro-invasive effect of IL-13Rα2. In conclusion, our results suggest that the high expression of IL-13Rα2 is significantly associated with the growth and metastasis of human glioma cells via the Scr/PI3K/Akt/mTOR pathway, while IL-13Rα2 may be a potential therapeutic target for glioma treatment.

Elucidating the impact of parthanatos-related microRNAs on the tumoral immune microenvironment and clinical outcome in low-grade gliomas.

Parthanatos, a cell death mechanism triggered by PARP-1 activation, is implicated in oncogenic processes, yet their role in low-grade gliomas (LGG) remains poorly understood. This research investigates Parthanatos-related miRNAs' prognostic and immunomodulatory potential, alongside their influence on therapeutic outcomes in LGGs. Comprehensive miRNA and mRNA profiles of LGG patients were extracted from TCGA and CGGA databases, integrating clinical parameters to identify Parthanatos-associated miRNAs. IHC data validated the expression levels of Parthanatos-related genes in glioma versus normal brain tissues. Protein-protein interaction networks and Spearman correlation analysis facilitated the identification of key miRNAs. Parthanatos-related miRNA indices (PMI) were screened using Lasso and assessed for their accuracy in predicting prognosis, comparing their associated potential molecular functions and heterogeneity of the immune microenvironment. Drug sensitivity was assessed between different groups and optimal therapeutic agents were predicted. Validate the expression levels of key miRNAs by qPCR. Ninety-one miRNAs significantly associated with Parthanatos were screened, through which a PMI prognosis model of nine miRNAs was constructed. The PMI score was able to independently predict the prognosis of patients with LGG, and the nomogram constructed based on the PMI provided a practical tool for clinical prediction of patient prognosis. The proportion of immune response was lower in patients in the high-risk group, and there were significant differences in drug sensitivity between different risk classes, while drugs such as Fasudil were identified as the most promising therapeutic agents for patients in the high-risk group. Our findings highlight the critical role of Parthanatos-associated miRNAs in the progression and treatment of LGG, offering novel insights into their prognostic value and therapeutic potential.

Surgical versus non-surgical treatment for pituitary apoplexy: A systematic review and meta-analysis.

BACKGROUND: Pituitary apoplexy is a rare disease caused by a sudden hemorrhage into or infarction of the pituitary gland. Its optimal management remains controversial. The aim of this study was to compare the outcomes of surgical and non-surgical treatments for pituitary apoplexy. METHODS: A systematic literature search was performed of MedLine, EmBase, the Cochrane Library, and the Web of Science for articles published between January 1992 and September 2014. Studies of the outcomes in consecutive patients that compared surgical intervention with non-surgical treatment for pituitary apoplexy were included. RESULTS: Six studies met the inclusion criteria. As compared to the non-surgically treated patients, surgically treated patients had a significantly higher rate of recovery of ocular palsy and visual field (both P<0.05). However, there was no significant difference in the recovery of visual acuity and pituitary function (P>0.05) between the two groups. CONCLUSIONS: The findings of our study suggest that surgical intervention should be advocated for pituitary apoplexy patients with visual field defects and ocular palsy.