Background and Objectives Glioblastoma (GBM) is the most common and lethal of intracranial tumors, which is characterized by extensive proliferation and the diffused invasion of tumor cells. MicroRNA‐193a‐5p (miR‐193a‐5p) have been demonstrated previously as a functional suppressor in the development and progression of various cancers. The current study aimed to investigate whether miR‐193a‐5p influences cell proliferation and migration through the mitogen‐activated protein kinase/extracellular signal‐regulated kinase signaling pathway by targeting neuro‐oncological ventral antigen 1 (NOVA1) in glioblastoma. Materials and Methods The miR‐193a‐5p expression was detected by quantitative real‐time polymerase chain reaction assay in GBM tissues and cell lines. Cell Counting Kit‐8 assay, colony formation analysis, wound‐healing, and transwell invasion assays were performed to evaluate cell proliferation, colony formation, migration, and invasion, respectively. Western blot analysis and luciferase reporter gene assay were performed to verify the downstream target gene of miR‐193a‐5p. Results The expression of miR‐193a‐5p was significantly downregulated in GBM tissues and cell lines. Kaplan‐Meier analysis showed that patients with low miR‐193a‐5p expression had a shorter disease‐free survival (P < 0.05). Functionally, miR‐193a‐5p overexpression dramatically suppressed the proliferation, colony formation, migration, and invasion in glioma cells. Bioinformatics prediction and a luciferase assay confirmed that NOVA1 was a direct functional target of miR‐193a‐5p. Moreover, ectopic expression of NOVA1 could partially reverse the inhibitory effects of miR‐193a‐5p on glioma cell proliferation, colony formation, migration, and invasion. NOVA1 overexpression abrogated the inhibitory effect of miR‐193a‐5p on the PTEN/PI3k/AKT pathway. Conclusion Taken together, our findings suggested that miR‐193a‐5p functions as a tumor suppressor in glioma cells by directly targeting NOVA1.

Background Glioma is a deadly and immunosuppressive brain tumour. Complement C1r subcomponent like (C1RL), a prognostic biomarker in several kinds of tumours, has attracted increasing attention from oncologists. However, the role of C1RL in glioma remains unclear. Methods Through analysis of 2120 glioma patients from 5 public datasets, the relationships between C1RL expression and clinicopathological characteristics were evaluated. Furthermore, the C1RL-associated genes were screened, and Gene Ontology (GO) analysis was conducted to investigate biological process enrichment. In addition, tumour purity, leukocyte infiltration and overall survival were evaluated based on C1RL expression. Results We found that C1RL expression was upregulated in glioblastoma (GBM), especially mesenchymal GBM and primary GBM. Increased C1RL expression accompanied the IDH1-wt phenotype in both lower grade glioma (LGG) and GBM. C1RL- associated genes were mainly enriched in biological processes related to the immune response. C1RL expression was also correlated with reduced tumour purity and increased M2 macrophage infiltration. Higher C1RL expression predicted unfavourable survival in patients with glioma and therapeutic resistance in GBM. Conclusions Our results imply that C1RL is involved in immunological activities and is an independent unfavourable prognostic biomarker in patients with glioma. C1RL is a potential clinical immunotherapeutic target for glioma treatment in the future.

Background. Glioblastoma (GBM) is a highly prevalent brain tumor characterized by high rates of morbidity, recurrence, and mortality. While temozolomide (TMZ) is commonly used as a first-line treatment for this cancer, the emergence of TMZ resistance limits its utility. The long noncoding RNA HOXA-AS2 reportedly drives GBM progression, but whether it can influence therapeutic resistance to TMZ has yet to be established. Methods. HOXA-AS2 expression was analyzed in TMZ-resistant and sensitive GBM tissue samples and cell lines by qPCR. A siRNA-based approach was used to knock down HOXA-AS2 in GBM cells, after which TMZ resistance was tested. Bioinformatics approaches were used to predict miRNA binding targets of HOXA-AS2, after which a series of luciferase reporter assay and rescue experiments with appropriate miRNA inhibitor/mimic constructs were performed to validate these predictions and to clarify the ability of HOXA-AS2 to regulate chemoresistant activity. Results. TMZ-resistant GBM patients and cell lines exhibited increased HOXA-AS2 expression that was correlated with worse overall survival. Knocking down HOXA-AS2 increased the sensitivity of resistant GBM cells to TMZ. miR-302a-3p was identified as a HOXA-AS2 target confirmed through luciferase reporter assays and rescue experiments, and IGF1 was further identified as a confirmed miR-302a-3p target. In addition, HOXA-AS2 knockdown resulted in a corresponding drop in IGF1 expression consistent with indirect regulation mediated by miR-302a-3p. Conclusion. In summary, these results highlight the role of HOXA-AS2 as a driver of TMZ resistance in GBM through its ability to regulate the miR-302a-3p/IGF1 signaling axis, highlighting this pathway as a promising target for the diagnosis, therapeutic sensitization, and/or treatment of affected patients.

Hypoxic injury to the brain is very intricate under the control of biochemical reactions induced by various factors and mechanisms. Long non-coding RNAs (lncRNAs) have already been revealed to affect pathological processes in the nervous system of different degrees. This research aimed to investigate the mechanisms implicated in hypoxic brain injury. β-Asarone mitigated the decrease of cell viability, superoxide dismutase activity, and mitochondrial membrane potential, as well as the increase of cell apoptosis, lactate dehydrogenase release, malondialdehyde content, and reactive oxidative species production by cobalt chloride. LncRNA ribonuclease P RNA component H1 (RPPH1) was discovered to be highly expressed in hypoxia-induced PC12 cells, and β-Asarone addition led to a decline in RPPH1 expression. RPPH1 overexpression reversed the effect of β-Asarone on hypoxia-induced injury in PC12 cells. Furthermore, we proved that RPPH1 could sponge miR-542-3p. Subsequently, death effector domain containing 2 (DEDD2) was proven as the downstream gene of RPPH1/miR-542-3p axis. Eventually, the whole regulation mechanism of RPPH1/miR-542-3p/DEDD2 axis was testified through rescue assays. The impacts of β-Asarone on hypoxia-induced PC12 cells could be countervailed by RPPH1 augment, which was also discovered to be neutralized in response to miR-542-3p overexpression or DEDD2 depletion. These findings offered a novel perspective for understanding neuroprotection.