The prognostic and immune significance of PLBD1 in pan-cancer and its roles in proliferation and invasion of glioma.

Cancer is a destructive disease and is currently the leading cause of major threats to human health. PLBD1 is a transcription factor that regulates phospholipid metabolism, but its role in tumors is unknown. We assessed pan-cancer expression, methylation, and mutation data of PLBD1 by multiple databases to investigate its clinical prognostic value. In addition, we examined the pan-cancer immunological signature of PLBD1, particularly in gliomas. Furthermore, we assessed the impact of PLBD1 knockdown on the proliferation and invasive capacity of glioma cells by in vitro experiments. Our results suggest that PLBD1 is highly expressed in multiple types of cancers, and it can serve as an independent prognostic factor for gliomas. In addition, we found that the epigenetic alterations of PLBD1 were highly heterogeneous in a variety of cancers, including gliomas, and that its high methylation was associated with poor prognosis in a broad range of cancers. Immunological profiling demonstrated that PLBD1 was significantly associated with immune cell infiltration and multiple immune checkpoints in gliomas and is a potential biomarker for gliomas. Furthermore, cellular experiments showed that knockdown of PLBD1 significantly inhibited the proliferation and invasive ability of glioma cells. In conclusion, PLBD1 is a potential tumor prognostic biomarker and immunotherapeutic target that plays a crucial role in glioma cell proliferation, invasion and immunotherapy.

Formyl Peptide Receptor 1 Inhibits Reparative Angiogenesis and Aggravates Neuroretinal Dysfunction in Ischemic Retinopathy.

PURPOSE: Ischemic retinopathy is the major cause of vision-threatening conditions. Inflammation plays an important role in the pathogenesis of ischemic retinopathy. Formyl peptide receptor 1 (FPR1) has been reported to be implicated in the regulation of inflammatory disorders. However, the role of FPR1 in the progression of ischemic retinal injury has not been fully explained. METHODS: The activation of FPR1 was measured by real-time PCR and western blotting in the retina of OIR. The effect of FPR1 on the expression of inflammatory cytokines and relevant pro-angiogenic factors was assessed between wild-type and FPR1-deficiency OIR mice. The impact of FPR1 on retinal angiogenesis was evaluated through quantifying retinal vaso-obliteration and neovascularization between FPR1+/+ and FPR1-/- OIR mice. At last, the neuronal effect of FPR1 on the ischemic retina was investigated by ERG between wild-type and FPR1-deficient OIR mice. RESULTS: The expression of FPR1 significantly increased in the retina of OIR. Furthermore, FPR1 deficiency downregulated pro-inflammatory and pro-angiogenic factors. Ablation of FPR1 suppressed the retinal pathological neovascularization and promoted reparative revascularization, ultimately improving retinal neural function after ischemic injury. CONCLUSION: In ischemic retinopathy, FPR1 aggravates inflammation and inhibits reparative angiogenesis to exacerbate neuronal dysfunction.

CREPT promotes glioma cell proliferation and invasion by activating Wnt/ß-catenin pathway and is a novel target of microRNA-596.

Cell cycle-related and expression elevated protein in tumor (CREPT) is emerging as a novel cancer-related gene that is dysregulated in many kinds of malignancies. However, the expression and biological role of CREPT in glioma remains unclear. In the present study, we aimed to explore the potential function and regulation mechanism of CREPT in glioma. Results showed that CRETP expression was significantly upregulated in glioma cell lines. Depletion of CREPT by siRNA-mediated gene silencing markedly decreased the proliferative and invasive capabilities of glioma cells. Bioinformatics analysis predicted CREPT as a target gene of microRNA-596 (miR-596), which was further verified by real-time quantitative polymerase chain reaction and Western blot analysis. miR-596 was significantly decreased in glioma tissues and cell lines, and inversely correlated with CREPT expression in clinical specimens. Knockdown of CREPT or overexpression of miR-596 significantly restricted the activation of Wnt/ß-catenin signaling in glioma cells. Moreover, overexpression of CREPT partially reversed the miR-596-mediated inhibitory effect on proliferation, invasion and Wnt/ß-catenin signaling in glioma cells. Overall, these results demonstrate that CREPT exerts an oncogenic role in glioma and its expression is regulated by miR-596. Our study highlights the important role miR-596/CREPT/Wnt/ß-catenin signaling axis may play in glioma.

MicroRNA-520e restricts the proliferation and invasion of glioma cells through the downregulation of Wnt/ß-catenin signaling by targeting fibroblast growth factor 19.

The abnormal expression of microRNAs (miRNAs) contributes to the development and progression of cancer. Recent studies have reported that miRNA-520e (miR-520e) is dysregulated in multiple cancers and is associated with tumor progression. However, the role of miR-520e in glioma has not been fully investigated. In this study, we investigated the function of miR-520e and its regulation by a molecular mechanism in gliomas. Our results showed that miR-520e expression was significantly downregulated in glioma tissues and cell lines. The overexpression of miR-520e repressed the proliferation, colony formation, and invasive potential of glioma cells, while the inhibition of miR-520e showed the opposite effect. The oncogenic gene fibroblast growth factor 19 (FGF19) was identified as a downstream target gene of miR-520e. The knockdown of FGF19 restricted the proliferation and invasion of glioma cells. Moreover, FGF19 knockdown or miR-520e overexpression decreased the expression of ß-catenin and suppressed the transcriptional activity of Wnt/ß-catenin signaling. Notably, the restoration of FGF19 expression partially reversed the miR-520e-mediated antitumor effect. In conclusion, our results demonstrate that miR-520e restricts the proliferation and invasion of glioma cells through the downregulation of FGF19/Wnt/ß-catenin signaling, highlighting an importance of miR-520e/FGF19/Wnt/ß-catenin signaling in gliomagenesis and suggesting miR-520e as a potential therapeutic target for gliomas.

Clinical Features, Intradural Transcavernous Surgical Management, and Outcomes of Giant Cavernous Sinus Hemangiomas: A Single-Institution Experience.

BACKGROUND: Cavernous sinus hemangiomas (CSHs) are rare vascular tumors. Stereotactic radiosurgery is an effective treatment for small CSHs. The optimal treatment for giant CSHs is controversial. This study reports advantages of a complete intradural transcavernous approach in total resection of CSHs. METHODS: Between January 2012 and January 2017, 15 patients with giant CSHs were treated surgically. All cases were evaluated with a contrast-enhanced magnetic resonance imaging scan and confirmed histopathologically. A complete intradural approach was used for all patients. Clinical manifestations, radiographic characteristics, operative techniques, and outcomes of patients were analyzed. RESULTS: Headache was the most common initial symptom, followed by decreased visual acuity and diplopia. Postoperative magnetic resonance imaging showed that gross total resection was achieved in 13 patients. Two patients had experienced total ipsilateral visual loss for several years before surgery; vision improved in all remaining patients with preoperative visual diminution. The most common early neurologic deficit was cranial nerve VI dysfunction, which was observed in 9 patients (60%; 5 new deficits). Only 2 patients (13.3%) experienced permanent morbidity on long-term follow-up. The early postoperative morbidity rate for cranial nerve III dysfunction was 33.3% (5 patients), and only 1 patient (6.7%) experienced permanent morbidity. Four patients (26.7%) had slight postoperative facial numbness. CONCLUSIONS: Surgical total resection is the primary and reasonable choice for giant CSHs. Microsurgical resection of giant CSHs through a completely intradural transcavernous approach is an alternative treatment option for giant CSHs.

Long noncoding RNA-RNCR3 overexpression deleteriously affects the growth of glioblastoma cells through miR-185-5p/Krüppel-like factor 16 axis.

Glioblastoma (GBM) is a devastating and highly aggressive tumor, which is apoptosis resistant and difficult to cure. Recently, long noncoding RNAs have been shown to play a pivotal role in GBM progression. Evidence has suggested that retinal noncoding RNA3 (RNCR3) is a GBM-associated noncoding RNA and is under-expressed in GBM. However, the function and mechanism of RNCR3 on GBM cell growth and apoptosis are still uncertain. In the current study, we found that the level of RNCR3 is decreased in U87, U251, U373, and A172 GBM cell lines when compared with the normal human astrocytes. Elevating long noncoding RNA RNCR3 expression markedly inhibits U87 and U251 cell survival and proliferation. Further studies indicated that RNCR3 overexpression promotes U87 and U251 cell apoptosis and activity caspase-3/7. Moreover, we found that RNCR3 overexpression promotes Krüppel-like factor 16 (KLF16) expression through inhibiting the level of miR-185-5p. We demonstrated that KLF16 is a direct target of miR-185-5p. An increased miR-185-5p level by a miR-185-5p mimic or decreased KLF16 by KLF16 small interfering RNA both reversed the function of RNCR3 overexpression on GBM cell growth and apoptosis. In summary, this study focuses on investigating the key molecular mechanisms of RNCR3 involved in GBM cell growth and apoptosis. Our data indicated that RNCR3 overexpression inhibits cell growth and induces its apoptosis through the miR-185-5p/KLF16 axis.

MicroRNA-409-3p Represses Glioma Cell Invasion and Proliferation by Targeting High-Mobility Group Nucleosome-Binding Domain 5.

Emerging evidence has suggested that aberrantly expressed microRNAs (miRNAs) are associated with glioma development and progression. The aberrant expression of miR-409-3p has been reported in several human cancers. However, little is known about the function of miR-409-3p in gliomas. The aim of this study was to investigate the specific role and molecular mechanism of miR-409-3p in gliomas. In the present study, we found that miR-409-3p was downregulated in glioma tissue and cell lines. Overexpression of miR-409-3p inhibited glioma cell invasion and proliferation, whereas suppression of miR-409-3p promoted glioma cell invasion and proliferation. High-mobility group nucleosome-binding domain 5 (HMGN5), a well-known oncogene in gliomas, was identified as a functional target of miR-409-3p using bioinformatics, dual-luciferase reporter assay, real-time quantitative polymerase chain reaction, and Western blot analysis. Furthermore, miR-409-3p was found to regulate the expression of matrix metalloproteinase 2 and cyclin D1. Restoration of HMGN5 expression significantly reversed the inhibitory effects of miR-409-3p overexpression on glioma cell invasion and proliferation. Taken together, our results suggest that miR-409-3p inhibits glioma cell invasion and proliferation by targeting HMGN5, representing a potential therapeutic target for glioma.