Reduced PTCH2 expression is associated with glioma development through its regulation of the PTEN/AKT signaling pathway.

Mutations in the human protein patched homolog (PTCH) gene have been demonstrated to be associated with cancer development in several types of malignancy. However, the underlying mechanism of PTCH-associated cancer development remains poorly understood, to the best of our knowledge. In the present study, the expression of PTCH2 in glioma tumor tissues from The Cancer Genome Atlas (TCGA) database and clinical patients with glioma were measured. Reduced expression levels of PTCH2 were observed in patients with glioma with poor prognose. In vitro, overexpression of PTCH2 significantly suppressed the proliferation and invasion of the glioma cell lines, LN229 and U87-MG. Mechanistically, PTCH2 upregulated the expression of tumor suppressor PTEN, thereby leading to the suppression of pro-survival AKT signals in glioma. Reduced expression of PTEN and enhanced expression of AKT promoted glioma development in vitro and in vivo. Blockade of PTCH2/AKT signals efficiently strengthened the anticancer effects of chemotherapy and prolonged the survival time in tumor-bearing mice, which provided a novel insight into potential treatment strategies for glioma in the clinic.

LncRNA LINC01094 contributes to glioma progression by modulating miR-224-5p/CHSY1 axis.

Glioma serves as the most common malignancy influencing modern people and is associated with severe morbidity and high mortality. Long non-coding RNAs (lncRNAs) as crucial regulators participate in multiple cancer progression. However, the role of lncRNA LINC01094 in the development of glioma remains unclear. Here, we aimed to explore the effect of lncRNA LINC01094 on the glioma progression and the underlying mechanism. Significantly, we revealed that the expression levels of LINC01094 were elevated in the glioma patient tissues compared to adjacent normal tissues. The LINC01094 expression was enhanced in the glioma cell lines. The depletion of LINC01094 inhibited cell viability and colony formation in the glioma cells. Meanwhile, the migration and invasion of glioma cells were impaired by the depletion of LINC01094. Mechanically, we identified that LINC01094 was able to sponge the miR-224-5p in the glioma cells and miR-224-5p inhibitor could reverse the effect of LINC01094 on glioma progression. In addition, miR-224-5p targeted CHSY1 and LINC01094 up-regulated CHSY1 by targeting miR-224-5p in the glioma cells. LINC01094 promoted glioma progression by the positive regulation of CHSY1. Moreover, tumorigenicity analysis showed that LINC01094 enhanced tumor growth of glioma in vivo. Thus, we conclude that lncRNA LINC01094 promotes glioma progression by modulating miR-224-5p/CHSY1 axis. Our finding provides new insights into the mechanism by which lncRNA LINC01094 contributes to the development of glioma, improving the understanding of lncRNA LINC01094 and glioma. LncRNA LINC01094, miR-224-5p, and CHSY1 may serve as potential targets for glioma.

Limb-bud and heart development (LBH) contributes to glioma progression in vitro and in vivo.

Glioma is the predominant brain malignancy and is correlated with high mortality and severe morbidity. The transcription factor limb-bud and heart (LBH) has been reported to be involved in the development of several cancers, although its role in glioma development remains elusive. Here, we examined the effect of LBH on glioma progression. The expression of LBH was increased in glioma samples from The Cancer Genome Atlas database, and upregulation of LBH was observed to be correlated with the poor survival of glioma patients. We also report that expression of LBH was elevated in clinical glioma tissues compared to adjacent normal tissues, and was also enhanced in glioma cell lines. LBH promotes proliferation and inhibits cell cycle arrest and apoptosis in glioma cells. In addition, LBH increased the migration and invasion of glioma cells in vitro. Moreover, tumorigenicity analysis revealed that LBH could promote the tumor growth of glioma cells in vivo. In conclusion, our findings suggest that LBH contributes to glioma progression in vitro and in vivo. Our findings provide new insights into the mechanism by which LBH promotes the development of glioma, improving our understanding of the correlation between LBH with cancer. LBH may have potential as a target for glioma therapy.

Galangin (GLN) Suppresses Proliferation, Migration, and Invasion of Human Glioblastoma Cells by Targeting Skp2-Induced Epithelial-Mesenchymal Transition (EMT).

BACKGROUND: Galangin (GLN), a pure natural flavonoid compound found in plants, has been shown to exert anti-cancer effects against multiple cancer types, including glioma. However, its underlying molecular mechanism remains unclear. Epithelial-to-mesenchymal transition (EMT) performs an important function in the genesis and development of cancer. Skp2, a pivotal component of SCFSkp2 E3 ubiquitin ligase, has been shown to function as an oncogene in GBM invasion that contributes to the EMT process. Thus, we explored whether GLN inhibited Skp2-mediated EMT and the mechanism underlying the Skp2 degradation pathway. METHODS: CCK-8 assay, wound healing assay and transwell assay were used to examine cell proliferation, migration, and invasion after treatment with or without GLN. RT-PCR and Western blotting analysis were performed to evaluate mRNA and protein expression, respectively. Co-immunoprecipitation was conducted to detect ubiquitinated Skp2 levels in vitro and in vivo after GLN treatment. Bioluminescence imaging was performed to examine the intracranial tumor size of U87 xenograft mice. Microscale thermophoresis (MST) experiment was used to detect interactions between Skp2 and GLN. RESULTS: GLN suppressed GBM cell growth, migration, and invasion, and also downregulated the expression of Skp2 and mesenchymal markers (Zeb1, N-cadherin, snail, vimentin) in vitro. Moreover, the overexpression of Skp2 in GBM cells decreased the effect of GLN on EMT. Furthermore, we demonstrated that GLN degraded skp2 protein through the ubiquitination proteasome pathway and directly interacted with skp2 protein, as shown through the MST assay. CONCLUSION: This study is the first to identify Skp2 as a novel target of GLN for the treatment of GBM and report of Skp2 protein degradation in a ubiquitination proteasome pathway. Results from our study indicated the potential of GLN for the treatment of GBM through ubiquitin-mediated degradation of Skp2.

The effect of cyclosporin a on ischemia-reperfusion damage in a mouse model of ischemic stroke.

OBJECTIVES: We aimed to investigate the protective effects of cyclosporin A (CsA) against ischemia-reperfusion (I/R) damage in a mouse ischemia model and the possible underlying mechanism. METHODS: Mice were divided equally into five groups: Sham, I/R, Vehicle, I/R plus CsA (10 mg/kg), and I/R plus CsA (20 mg/kg). Nerve function scores, infarct volume, brain water content, and Evans blue (EB) leakage were evaluated, and western blotting was performed to analyze the changes in CypA, p-Akt, NF-κB, MMP-9, and Claudin-5 expression. RESULTS: CsA can attenuate I/R damage in a mouse ischemic stroke model, as indicated by improved neurological function scores and decreased infarct volume, brain water content, and EB leakage. Additionally, high-dose CsA showed better protective effects than low-dose. The molecular mechanisms underlying the effects of CsA were explored, and it was found that CsA could inhibit the increase in CypA, p-Akt, NF-κB, and MMP-9 protein expression after middle cerebral artery occlusion, while Claudin-5 expression was decreased. DISCUSSION: CsA showed potential as a neuroprotective drug for the treatment of ischemic stroke patients; besides interfering with the typical NF-κB signaling pathway, the Akt pathway may also be involved in the effects of CsA.

The SDF-1 rs1801157 Polymorphism is Associated with Cancer Risk: An Update Pooled Analysis and FPRP Test of 17,876 Participants.

The stromal cell derived factor-1 (SDF-1) rs1801157 gene polymorphism has been implicated in susceptibility to cancer, but the results were inconclusive. The current study was to precisely investigate the association between SDF-1 rs1801157 polymorphism and cancer risk using meta-analysis and the false positive report probability (FPRP) test. All 17,876 participants were included in the study. The meta-analysis results indicated a significant association between the SDF-1 rs1801157 polymorphism and cancer risk. By subgroup analyses, the results detected that the SDF-1 rs1801157 polymorphism was associated with cancer susceptibility among Asians and Caucasians. Additionally, we also found significant associations between the SDF-1 rs1801157 polymorphism and susceptibility to different types of cancer. However, to avoid a "false positive report", we further investigated the significant associations observed in the present meta-analysis using the FPRP test. Interestingly, the results of the FPRP test indicated that only 4 gene models were truly associated with cancer risk, especially in Asians. Moreover, we confirmed that the SDF-1 rs1801157 gene polymorphism was only associated with lung and urologic cancer risk. In summary, this study suggested that the SDF-1 rs1801157 polymorphism may serve as a risk factor for cancer development among Asians, especially an increased risk of urologic and lung cancers.