Predictive Panel for Immunotherapy in Low-Grade Glioma.

Background: The main treatment of low-grade glioma (LGG) is still surgical resection followed by radiotherapy and/or chemotherapy, which has certain limitations, including side effects and drug resistance. Immunotherapy is a promising treatment for LGG, but it is generally hindered by the tumor microenvironment with the limited expression of tumor antigens.

Methods: We integrated RNA sequencing data sets and clinical information and conducted consistent cluster analysis to explore the most suitable patients for immune checkpoint therapy.

Membrane-bound transcription factor LRRC4 inhibits glioblastoma cell motility.

Membrane-bound transcription factors (MTFs) have been observed in many types of organisms, such as plants, animals and microorganisms. However, the routes of MTF nuclear translocation are not well understood. Here, we reported that LRRC4 is a novel MTF that translocates to the nucleus as a full-length protein via endoplasmic reticulum-Golgi transport, which is different from the previously described nuclear entry mechanism.

LncRNA , a Ferroptosis Suppressor and Prognositic Signature for GBM.

is a long noncoding RNA also known as long intergenic nonprotein coding RNA 1272 (). The known reports showed that functions as an onco-lncRNA or a suppressor lncRNA by suppressing miRNA in colorectal cancer, gastric cancer and lung cancer. In this study, we first found that , as an onco-lncRNA, alleviates the ferroptosis driven by mutant and promotes mutant -mediated GBM proliferation.

Circular RNA Sequencing Reveals Serum Exosome Circular RNA Panel for High-Grade Astrocytoma Diagnosis.

Background: Although major advances have been made in the histopathological diagnosis of high-grade astrocytoma (HGA), methods for effective and noninvasive diagnosis remain largely unknown. Exosomes can cross the blood-brain barrier and are readily accessible in human biofluids, making them promising biomarkers for HGA. Circular RNAs (circRNAs) have potential as tumor biomarkers owing to their stability, conservation, and tissue specificity.

LRRC4 mediates the formation of circular RNA CD44 to inhibitGBM cell proliferation.

Mounting evidence reveals that dysregulation of circular RNAs (circRNAs) is involved in the development of glioblastoma. Leucine-rich repeat-containing 4 (LRRC4) has been shown to suppress tumors in glioblastoma. However, whether LRRC4 can regulate the formation of circRNA is not yet understood.

Nestin Is Required for Spindle Assembly and Cell-Cycle Progression in Glioblastoma Cells.

Nestin, a class IV intermediate filament protein, is generally considered as a putative marker of neural stem and progenitor cells in the central nervous system. Glioma is a common type of adult brain tumors, and glioblastoma (GBM) represents the most aggressive form of glioma. Here, we report that Nestin expression is significantly upregulated in human GBM, compared with other types of glioma.

LRRC4 functions as a neuron-protective role in experimental autoimmune encephalomyelitis.

Background: Leucine rich repeat containing 4 (LRRC4), also known as netrin-G ligand-2 (NGL-2), belongs to the superfamily of LRR proteins and serves as a receptor for netrin-G2. LRRC4 regulates the formation of excitatory synapses and promotes axon differentiation. Mutations in LRRC4 occur in Autism Spectrum Disorder (ASD) and intellectual disability.

Corrigendum: Coagulation Factor X Regulated by CASC2c Recruited Macrophages and Induced M2 Polarization in Glioblastoma Multiforme.

[This corrects the article DOI: 10.3389/fimmu.2018.

Leucine-rich repeat containing 4 act as an autophagy inhibitor that restores sensitivity of glioblastoma to temozolomide.

Temozolomide (TMZ) insensitivity and resistance are major causes of treatment failure and poor prognosis for GBM patients. Here, we identify LRRC4 as a novel autophagy inhibitor that restores the sensitivity of GBMs to TMZ. LRRC4 was associated with the DEPTOR/mTOR complex, and this interaction resulted in autophagy inhibition.

lncRNA RMST Suppressed GBM Cell Mitophagy through Enhancing FUS SUMOylation.

Long non-coding RNAs (lncRNAs) play a significant role in post-translational modifications of proteins, yet the importance of lncRNAs for SUMOylation is unknown. rhabdomyosarcoma 2 associated transcript (RMST) expression in glioma tissues and normal brain tissues was measured by quantitative real-time PCR and in situ hybridization. The functional roles of RMST in astrocytomas were demonstrated by a series of in vitro experiments.

Hypermethylated gene ANKDD1A is a candidate tumor suppressor that interacts with FIH1 and decreases HIF1α stability to inhibit cell autophagy in the glioblastoma multiforme hypoxia microenvironment.

Ectopic epigenetic mechanisms play important roles in facilitating tumorigenesis. Here, we first demonstrated that ANKDD1A is a functional tumor suppressor gene, especially in the hypoxia microenvironment. ANKDD1A directly interacts with FIH1 and inhibits the transcriptional activity of HIF1α by upregulating FIH1.

LINC00470 Coordinates the Epigenetic Regulation of ELFN2 to Distract GBM Cell Autophagy.

The epigenetics and genomics of glioblastoma (GBM) are complicated. Previous reports indicate that ELFN2 is widely distributed in the cerebral cortex neurons, striatum, and hippocampus cone and in granular cells. However, the function and mechanism of ELFN2, particularly in GBM, have rarely been explored.

Coagulation Factor X Regulated by CASC2c Recruited Macrophages and Induced M2 Polarization in Glioblastoma Multiforme.

Tumor-associated macrophages (TAMs) constitute a major component of inflammatory cells in the glioblastoma multiforme (GBM) tumor microenvironment. TAMs have been implicated in GBM angiogenesis, invasion, local tumor recurrence, and immunosuppression. Coagulation factor X (FX) is a vitamin K-dependent plasma protein that plays a role in the regulation of blood coagulation.

A cytoplasmic long noncoding RNA LINC00470 as a new AKT activator to mediate glioblastoma cell autophagy.

Background: Despite the overwhelming number of investigations on AKT, little is known about lncRNA on AKT regulation, especially in GBM cells.

Methods: RNA-binding protein immunoprecipitation assay (RIP) and RNA pulldown were used to confirm the binding of LINC00470 and fused in sarcoma (FUS). Confocal imaging, co-immunoprecipitation (Co-IP) and GST pulldown assays were used to detect the interaction between FUS and AKT.

SIX3, a tumor suppressor, inhibits astrocytoma tumorigenesis by transcriptional repression of AURKA/B.

Background: SIX homeobox 3 (SIX3) is a member of the sine oculis homeobox transcription factor family. It plays a vital role in the nervous system development. Our previous study showed that the SIX3 gene is hypermethylated, and its expression is decreased in astrocytoma, but the role of SIX3 remains unknown.

Low expression of miR-381 is a favorite prognosis factor and enhances the chemosensitivity of osteosarcoma.

Osteosarcoma (OS) is the most common primary bone malignancy with a poor prognosis for all races and both sexes. In this study, we found that miR-381 is a positive prognosis factor for OS patients that OS patients with a low expression of miR-381 had a longer survival time after surgical intervention, and miR-381 expression promotes MG-63 cell proliferation and cell invasion ability. Our results also showed a strong negative correlation between the expression of miR-381 and LRRC4 (brain relative specific expression gene) in OS tissues.

miR-101 reverses hypomethylation of the PRDM16 promoter to disrupt mitochondrial function in astrocytoma cells.

Our previous report identified PR domain containing 16 (PRDM16), a member of the PR-domain gene family, as a new methylation associated gene in astrocytoma cells. This previous study also reported that miR-101 is a tumor suppressor in glioma. The present study confirms that PRDM16 is a hypomethylated gene that can be overexpressed in astrocytoma patients and demonstrates that the hypomethylation status of the PRDM16 promoter can predict poor prognoses for astrocytoma patients.