MiR-222-3p inhibits formation of medulloblastoma stem-like cells by targeting Notch2/c-myc signaling pathway.

BACKGROUND: Medulloblastoma (MB) is an embryonal tumor of the cerebellum, which commonly occurs in childhood. Herein, we investigated the effects of miR-222-3p on the formation of MB stem-like cells via the Notch2/c-myc pathway. METHODS: Quantitative real-time PCR (qRT-PCR) or western blotting was performed to determine the expression of miR-222-3p and Notch2, c-myc, proliferating cell nuclear antigen (PCNA), and caspase-3. Luciferase reporter gene, RNA immunoprecipitation (RIP), and RNA pull-down assay were applied to confirm the interaction between miR-222-3p and Notch2. Cell growth was examined by Cell Counting Kit-8. Cell cycle distribution and the number of stem cell marker CD133+ cells were examined using flow cytometry. The sphere formation assay was performed. RESULTS: miR-222-3p expression was decreased and Notch2 expression was increased in human medulloblastoma cells. miR-222-3p overexpression inhibited cell viability and the sphere formation, induced cell cycle arrest, decreased the number of CD133+ cells, and up-regulated caspase-3 expression and down-regulated PCNA, Notch2, and c-myc expression. However, Notch2 overexpression counteracted these effects of miR-222-3p overexpression. Simultaneous overexpression of Notch2 and miR-222-3p increased the c-myc promoter-luciferase activity which was decreased by miR-222-3p overexpression. Luciferase reporter gene, RIP, and RNA pull-down assay revealed that miR-222-3p targeted Notch2. CONCLUSION: MiR-222-3p suppressed cell viability, altered cell cycle distribution, and inhibited the formation of MB stem-like cells via the Notch2/c-myc pathway.

Endoscopic Far-Lateral Supracerebellar Infratentorial Approach for Petroclival Region Meningioma: Surgical Technique and Clinical Experience.

BACKGROUND: The management of petroclival region meningioma remains the ultimate achievement in neurosurgery, because of the formidable technical challenges involved. OBJECTIVE: To describe the technique and feasibility of the purely endoscopic far-lateral supracerebellar infratentorial approach (EF-SCITA) for the treatment of petroclival region meningiomas. METHODS: We reviewed the clinical data of 10 consecutive cases of petroclival region meningiomas treated with the EF-SCITA from August 2018 to August 2020. The clinical outcomes were analyzed. The patient was placed in the lateral position, and then, a "C" shaped incision and craniotomy with exposed sigmoid and transverse sinuses were performed. With the endoscopic holder, endoscopic procedures were performed using standard 2-hand microsurgical techniques. Whether the tentorium or Meckel cave was handled depended on the tumor extension. RESULTS: The mean diameter was 45 × 25 mm. Dizziness and headache were the main symptoms. All 10 patients achieved gross total or subtotal resection (Petroclival Meningioma Grade I-III) with good neurological outcomes. The EF-SCITA provides satisfactory, direct exposure to the petroclival region. Cranial nerve deficits are the main postoperative complications. Two patients had a trochlear nerve injury, 3 patients had transient facial paralysis, and 2 patients had oculomotor paralysis (1 total and 1 incomplete), but both of them recovered during the follow-up period. One patient experienced an ipsilateral superior cerebellar artery infarction, and another patient had transient hemiparesis. CONCLUSION: The EF-SCITA is effective for most petroclival region meningiomas, except for the cavernous sinus type. This approach simplifies craniotomy procedures, omits burdensome petrosectomy, and avoids crossing posterior neurovascular structures.

Giant Intraparenchymal Meningioma in a Female Child: Case Report and Literature Review.

BACKGROUND: Intraparenchymal meningiomas without dural attachment are extremely rare, especially in female children. To our knowledge, fibrous intraparenchymal meningioma located in the temporal lobe has never been reported in female children. The significance in the differential diagnosis of lesions in the temporal lobe should be emphasized. CASE PRESENTATION: A 12-year-old girl was admitted to our hospital, complaining of recurrent generalized seizures for 2 months. Magnetic resonance imaging demonstrated a solid lesion located in the temporal lobe. The lesion underwent gross total resection. Histopathological examination indicated that the lesion was a fibrous meningioma. Postoperative rehabilitation was uneventful. CONCLUSION: This case report presents an extremely unusual intraparenchymal fibrous meningioma of the temporal lobe with peritumoral edema and reviewed 21 intraparenchymal meningioma cases in children and to discuss the clinical presentation and treatment, differential diagnosis, and radiological features.

Decreased expression of circ_0020397 in intracranial aneurysms may be contributing to decreased vascular smooth muscle cell proliferation via increased expression of miR-138 and subsequent decreased KDR expression.

Dysfunction of vascular smooth muscle cells (VSMCs) mediates intracranial aneurysm (IA). KDR is reported to alleviate IA progression via promoting VSMC proliferation, while the upstream regulators are still unclear. Arterial wall tissues at the aneurysm site from 12 patients were obtained. The real-time PCR result indicated that circRNA_0020397 was down-regulated, but miR-138 was up-regulated in artery wall tissues and cells of IA. Overexpressed circRNA_0020397 promoted proliferation of human umbilical artery SMCs. MiR-138 negatively regulated KDR via binding with 3'UTR of KDR mRNA. The expression of circRNA_0020397 was negatively correlated with miR-138. In conclusion, our findings demonstrated that decreased expression of circRNA_0020397 in IA may contribute to the decreased VSMC proliferation via increasing miR-138 expression and subsequently decreasing KDR expression.

Endothelial Cells Promote Formation of Medulloblastoma Stem-Like Cells via Notch Pathway Activation.

The aim of the study is to investigate whether endothelial cells (ECs) promoted the capacity of stem-like cell formation in medulloblastoma (MB) and whether the mechanism of action was associated with mediation of Notch signaling pathway. Co-culture experiment was conducted to particularly understand the potential role of ECs in promoting phenotype and gene expression of MB stem-like cells. Self-renewal capacity and tumor cell population were measured by sphere-forming assay and flow cytometry, respectively. To further clarify the effects of ECs on the formation of MB stem-like cells, the expression of genes and protein in MB stem-like cells (CCND1, CDK6, c-MYC, and Bmi-1) and Notch (Notch2, Jagged 1, Hes-1, and Hey-2) was quantified by quantitative real-time PCR (qRT-PCR) and western blot, respectively. Also, observed mediation of ECs in regulation of tumor cell stemness by Notch activation was observed when the co-cultures were treated with γ-secretase inhibitor (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT)). Further investigation was conducted for the effects of ECs on the tumorigenesis in vivo of MB cells when co-cultures were inoculated into a nude mouse after treated with DAPT. Afterwards, tumor size and volume were measured. The sphere-forming rate and cell ratio of stem-like cells were significantly increased. Furthermore, the expression of genes and protein in stem-like cells and Notch was obviously upregulated although treated with γ-secretase inhibitor. Moreover, tumor size and volume were dramatically magnified. This study revealed that Notch pathway activation played a key role in the formation of stem-like cells in MB and had valuable meaning for further investigation of targeted therapies.