Quanmin Nie

C-Myc negatively controls the tumor suppressor PTEN by upregulating miR-26a in glioblastoma multiforme cells

The c-Myc oncogene is amplified in many tumor types. It is an important regulator of cell proliferation and has been linked to altered miRNA expression, suggesting that c-Myc-regulated miRNAs might contribute to tumor progression. Although miR-26a has been reported to be upregulated in glioblastoma multiforme (GBM), the mechanism has not been established. We have shown that ectopic expression of miR-26a influenced cell proliferation by targeting PTEN, a tumor suppressor gene that is inactivated in many common malignancies, including GBM. Our findings suggest that c-Myc modulates genes associated with oncogenesis in GBM through deregulation of miRNAs via the c-Myc-miR-26a-PTEN signaling pathway. This may be of clinical relevance.

Overexpression of isocitrate dehydrogenase-1R132H enhances the proliferation of A172 glioma cells via aerobic glycolysis

Gliomas are the most common type of primary malignancy of the central nervous system. The identification of mutations in the gene encoding isocitrate dehydrogenase‑1 (IDH1) represents a key area of investigation in studies on glioma. The IDH1R132H mutation is a heterozygous point mutation, which affects the amino acid arginine at position 132, however, the metabolic importance of this mutation in tumor cell growth remains to be elucidated. In the present study, A172 glioma cell lines stably overexpressing either wild‑type IDH1 or IDH1R132H were produced. The results demonstrated that the IDH1R132H mutation enhanced the proliferation of the A172 glioma cells in vitro. Furthermore, IDH1R132H performed this function by elevating the expression levels of hypoxia inducible factor‑1α, leading to an increase in the expression levels of the key glycolytic enzymes, glucose transporter 1 and hexokinase 2. Therefore, the metabolism was shifted towards aerobic glycolysis, leading to an increase in glucose uptake and lactate production. These findings demonstrated that the IDH1R132H molecular target was involved in orchestrating the Warburg effect in mutant IDH1R132H glioma cells.

Silencing of Id2 attenuates hypoxia/ischemia-induced neuronal injury via inhibition of neuronal apoptosis.

Cerebral ischemic stroke has long been recognized as a prevalent and serious neurological disease that was associated with high mortality and morbidity. However, the current therapeutic protocols remain suboptimal with major mechanisms underlying stroke urgently warranted. Inhibitor of DNA binding/differentiation 2 (Id2) is found to be up-regulated in neuronal cells following hypoxia/ischemia (H/I). This study was aimed to investigate whether knockdown of Id2 in neuronal cells could protect them from hypoxic and ischemic injury both in vitro and in vivo. Flow cytometric analysis was employed to assess neuronal apoptosis in CoCl2-treated neuroblastoma B35 cells engineered to overexpress or knockdown Id2 expression. In vivo knockdown of Id2 was performed in Sprague-Dawley rats by a single intracerebroventricular injection of Cy3-labeled and cholesterol-modified Id2-siRNA. We found that knockdown of Id2 attenuated H/I-induced neuronal apoptosis in vitro while overexpression of Id2 produced an opposite effect. In a rat model of middle cerebral artery occlusion (MCAO), in vivo knockdown of Id2 significantly improved neurological deficits, reduced the volume of ischemic infarction and diminished the neuronal apoptosis in the penumbra area. Double immunofluorescence staining showed less co-localization of retinoblastoma tumor suppressor protein (Rb)-Id2 but greater co-localization of Rb-E2F1 in the penumbra area. Cell cycle assay further demonstrated that Id2 knockdown induced G0/G1 cell cycle arrest in CoCl2-treated B35 cells. The present data support the implication of Id2 in the modulation of H/I-induced neuronal apoptosis and may provide a potential therapeutic option to protect brain tissues from ischemic injury by inhibition of its expression.

Overexpression of FoxO3a is associated with glioblastoma progression and predicts poor patient prognosis

Forkhead transcription factor FoxO3a has been reported to have ambiguous functions and distinct mechanisms in various solid tumors, including glioblastoma (GBM). Although a preliminary analysis of a small sample of patients indicated that FoxO3a aberrations in glioma might be related to aggressive clinical behavior, the clinical significance of FoxO3a in glioblastoma remains unclear. We investigated the expression of FoxO3a in a cohort of 91 glioblastoma specimens and analyzed the correlations of protein expression with patient prognosis. Furthermore, the functional impact of FoxO3a on GBM progression and the underlying mechanisms of FoxO3a regulation were explored in a series of in vitro and in vivo assays. FoxO3a expression was elevated in glioblastoma tissues, and high nuclear FoxO3a expression in human GBM tissues was associated with poor prognosis. Moreover, knockdown of FoxO3a significantly reduced the colony formation and invasion ability of GBM cells, whereas overexpression of FoxO3a promoted the colony formation and invasion ability. The results of in vivo GBM models further confirmed that FoxO3a knockdown inhibited GBM progression. More, the pro‐oncogenic effects of FoxO3a in GBM were mediated by the activation of c‐Myc, microtubule‐associated protein 1 light chain 3 beta (LC3B) and Beclin1 in a mixed‐lineage leukemia 2 (MLL2)‐dependent manner. These findings suggest that high FoxO3a expression is associated with glioblastoma progression and that FoxO3a independently indicates poor prognosis in patients. FoxO3a might be a novel prognostic biomarker or a potential therapeutic target in glioblastoma.

Hypoxia/ischemia up-regulates Id2 expression in neuronal cells in vivo and in vitro.

Inhibitor of DNA binding/differentiation 2 (Id2) belongs to a family of transcriptional modulators characterized by a helix-loop-helix (HLH) motif that lacks the basic amino acid domain necessary to bind DNA. The aim of this study was to obtain a better understanding of the role of Id2 in hypoxia/ischemia (H/I)-induced neuronal apoptosis. Following H/I induction in a rat model of middle cerebral artery occlusion (MCAO)/reperfusion, the number of TUNEL-positive cells in cerebral cortices of the penumbra area increased gradually, while the Id2 mRNA and protein expression were also significantly up-regulated. The hypoxia-mimetic, cobalt chloride (CoCl2)-treated rat neuroblastoma B35 cell line also demonstrated enhanced Id2 mRNA and protein expression as well as increased number of cells in the sub-G1 populations after H/I exposure. Consistently, the expression of Bax, a proapoptotic protein, was also up-regulated in vivo and in vitro. Moreover, triple immunofluorescence demonstrated the obvious co-localization of Id2, TUNEL and NeuN in neurons of the penumbra area. These data suggest that H/I up-regulates Id2 expression in neuronal cells, and Id2 might play an important role in H/I-induced neuronal apoptosis.

Early-stage hemangioblastoma presenting as a small lesion with significant edema in the cerebellum.

Hemangioblastomas are benign tumors that are frequently associated with peritumoral cysts; however, their early characteristics before cyst formation remain unclear. In this article, the authors present a novel case of a cerebellar hemangioblastoma presenting as a small solid lesion with significant edema. Surgery was performed to resect the tumor, and a follow-up magnetic resonance imaging scan revealed complete excision of the mass and resolution of the cerebellar edema. Histological examination confirmed that the lesion was a hemangioblastoma. This is the only report in the literature to describe the imaging and histopathologic characteristics of an initial hemangioblastoma in the cerebellum.

Feasibility of three-dimensional ultrashort echo time magnetic resonance imaging at 1.5 T for the diagnosis of skull fractures

ObjectivesTo investigate the feasibility of ultrashort echo time (UTE) magnetic resonance imaging (MRI) for the diagnosis of skull fractures.MethodsThe skull fracture models of ten Bama pigs and 364 patients with craniocerebral trauma were subjected to computed tomography (CT), UTE and conventional MRI sequences. The accuracy of UTE imaging in skull fracture diagnosis was analysed using receiver operating characteristic (ROC) curve analysis, McNemar’s test and Kappa values. Differences among CT, UTE imaging and anatomical measurement (AM) values for linear fractures (LFs) and depressed fractures (DFs) were compared using one-way ANOVA and a paired-samples t-test.ResultsUTE imaging clearly demonstrated skull structures and fractures. The accuracy, validity and reliability of UTE MRI were excellent, with no significant differences between expert readings (P > 0.05; Kappa, 0.899). The values obtained for 42 LFs and 13 DFs in the ten specimens were not significantly different among CT, UTE MRI and AMs, while those obtained for 55 LFs and ten DFs in 44 patients were not significantly different between CT and UTE MRI (P > 0.05).ConclusionsUTE MRI sequences are feasible for the evaluation of skull structures and fractures, with no radiation exposure, particularly for paediatric and pregnant patients.Key Points• Despite ionising radiation, CT is standard for skull fracture assessment.• Conventional MRI cannot depict skull structures.• 3D-UTE sequences clearly demonstrate skull structures and fractures.• UTE plus conventional MRI are superior to CT in craniocerebral trauma assessment.• Paediatric and pregnant patients will benefit from this imaging modality.

Cerebral lipiodol embolism following abdomen trauma in a patient with hepatocellular carcinoma treated with transcatheter arterial chemoembolization

Transcatheter arterial chemoembolization (TACE) is commonly used to treat large unresectable hepatocellular carcinoma (HCC) or multiple HCCs. With TACE, an iodized oil-based contrast medium, such as lipiodol, mixed with a chemotherapeutic agent is injected into a feeding artery of the tumor. Cerebral lipiodol embolism (CLE) is considered an extremely rare complication of TACE [1]. Although cerebral fat embolism is well known to occur in patients with acute traumatic long bone fractures, there has been no previous report of CLE associated with trauma.