A Novel Tumor-Suppressor, CDH18, Inhibits Glioma Cell Invasiveness Via UQCRC2 and Correlates with the Prognosis of Glioma Patients.

BACKGROUND/AIMS: CDH18 (cadherin 18) is specifically expressed in the central nervous system and associated with various neuropsychiatric disorders. In this study, the role of CDH18 in glioma carcinogenesis and progression was investigated. METHODS: The expression of CDH18 and its prognostic value in patients with gliomas were analyzed in public database and validated by real-time PCR/immunohistochemical staining (IHC) in our cohort. CCK-8 assay, transwell migration assay, wound healing assay, clonogenic assay and tumorigenicity assay were used to compare the proliferation, invasion and migration ability of glioma cells with different expressions of CDH18. iTRAQ-based quantitative proteomic analysis were used to reveal the downstream target of CDH18. Rescue experiments were conducted to further validate the relationship between UQCRC2 and CDH18. RESULTS: The expression of CDH18 was depressed in a ladder-like pattern from normal tissues to WHO IV gliomas, and was an independent prognostic factor in TCGA (The Cancer Genome Atlas), CGGA (the Chinese glioma genome-atlas) and our glioma cohorts (n=453). Functional experiments in vitro and in vivo demonstrated that CDH18 inhibited invasion/migration, enhanced chemoresistance and suppressed tumorigenicity of glioma cells. UQCRC2 was identified as the downstream target of CDH18 by proteomic analysis. The expression of UQCRC2 was gradually absent as the WHO grades of gliomas escalated and was positively correlated with the expression of CDH18. Furthermore, in vitro assays demonstrated that down-regulation of UQCRC2 partly reversed the inhibition of invasion/migration ability and chemoresistance in CDH18 overexpressed glioma cell lines. Survival analysis demonstrated that combined CDH18/UQCRC2 biomarkers significantly influenced the prognosis of glioma patients. CONCLUSIONS: The present research demonstrated that CDH18 exerted its tumor-suppressor role via UQCRC2 in glioma cells and CDH18 might serve as a therapeutic target for treating gliomas.

Regulation of UHRF1 by microRNA-378 modulates medulloblastoma cell proliferation and apoptosis.

A previous study revealed that ubiquitin-like with PHD and RING finger domains 1 (UHRF1) promoted cell proliferation and was a potential biomarker in medulloblastoma (MB). In the present study, we reported that miR-378 inhibited the expression of UHRF1 to affect the proliferation of MB through competitive binding to the same region of its 3'-UTR. We found that the expression of miR-378 was significantly downregulated in MB tissues and inversely correlated with the expression of UHRF1. Western blot analysis revealed that overexpression of miR-378 led to the suppression of UHRF1. Moreover, a dual-luciferase assay demonstrated that miR-378 negatively regulated the activity of target gene UHRF1 by binding to its 3'-UTR. An in vitro assay revealed that overexpression of miR-378 suppressed MB cell proliferation and promoted cell apoptosis. Ectopic expression of UHRF1 rescued miR-378-suppressed cell proliferation and miR-378-promoted cell apoptosis. Collectively, the present study demonstrated that miR-378 could inhibit the proliferation of MB by downregulation of UHRF1 and act as a potential therapeutic target against MB.

Clinicopathological analysis of HOXD4 expression in diffuse gliomas and its correlation with IDH mutations and 1p/19q co-deletion.

BACKGROUNDS: HOX (homologous box) is known as the dominant gene of vertebrate growth and cell differentiation. Abnormal expression of HOX gene in various tumors has attracted the attention of scholars. As a component of HOX clusters, HOXD4 plays a controversial role in the tumorigenesis of central nervous system. RESULTS: The data demonstrated that and the results demonstrated that HOXD4 was overexpressed in glioma tissues compared to that of normal brain tissues. patients with high HOXD4 expression had a significant shorter survival than those with low HOXD4 expression in total glioma cohort (p<0.001), WHO Grade II cohort (p=0.003) and Grade III cohort (p<0.001), but not in Grade IV cohort when OS (overall survival) was analyzed (p=0.216). The findings were confirmed by the large-scale omics data analysis including lower-grade glioma (LGG) and glioblastoma multiforme (GBM) in TCGA (the cancer genome atlas) and CGGA (Chinese glioma genome atlas). Moreover, it was revealed that the expression of HOXD4 have a significant impact on the OS of Grade IV glioma with IDH wild-type and 1p/19q intact according to TCGA data. METHODS: Clinicopathological analysis of HOXD4 expression in 453 glioma patients was performed in the current study. Expression of HOXD4 was evaluated by qPCR and immunohistochemical (IHC) staining. Univariate and multivariate analysis were conducted to investigate the prognostic role of HOXD4 in glioma patients. CONCLUSIONS: Expression of HOXD4 was closely related to the clinical outcomes of patients with gliomas, and HOXD4 may be a potential prognostic biomarker of gliomas.

Intracranial solitary fibrous tumors: A report of two cases and a review of the literature.

Solitary fibrous tumors (SFTs) are uncommon, with the pleura as a site of predilection. Central nervous system SFTs, particularly intracranial SFTs, are extremely rare. The lesions are generally benign and localized, and surgery is the main therapeutic solution. The current study reports the cases of a patient who presented with right haunch pain, right leg weakness and paresthesias for several months, and a patient with a history of unexpected loss of consciousness. Magnetic resonance imaging revealed the presence of lesions, with a spindle cell morphology evident on pathological examination. The immunohistochemical examination demonstrated a strong immunoreaction for cluster of differentiation 34, which supported the diagnosis of an SFT. Following a near-total resection, the patients had a good neural prognosis. The present study also provides a literature review, discussing the imageological and pathological characteristics of SFT, and the diagnostic methods that aid in distinguishing the entity from other spindle-cell central nervous system tumors.