CircRNA Circ-ITCH Inhibits the Proliferation and Invasion of Glioma Cells Through Targeting the miR-106a-5p/SASH1 Axis.

Circ-ITCH, a novel circRNA, was generated from several exons of itchy E3 ubiquitin protein ligase (ITCH). Recently, circ-ITCH has been demonstrated to be involved in cancer development. However, there have been few investigations on the specific role of circ-ITCH in glioma. In this study, we performed quantitative real-time polymerase chain reaction analysis and identified that circ-ITCH was significantly downregulated in glioma tissues and cell lines. The function assays showed that upregulation of circ-ITCH inhibited glioma cell proliferation and invasion in vitro as well as reduced cell growth in vivo. Moreover, miR-106a-5p was found serving as a target of circ-ITCH and miR-106a-5p mimics could reverse the inhibitory effect of circ-ITCH on glioma cell proliferation and invasion. We also revealed that circ-ITCH increased SASH1 expression by sponging miR-106a-5p in glioma cells. In addition, SASH1 downregulation could abrogate the suppressive effect of circ-ITCH on glioma progression. Taken together, our results suggested that circ-ITCH could suppress glioma cell proliferation and invasion via regulating the miR-106a-5p/SASH1 axis, elucidating a novel molecular target for glioma treatment.

The long noncoding RNA ZFAS1 promotes the progression of glioma by regulating the miR-150-5p/PLP2 axis.

Numerous studies have reported that long noncoding RNA (lncRNA) dysregulation is involved in the progression of many malignant tumors, including glioma. The lncRNA ZNFX1 antisense RNA 1 (ZFAS1) plays an oncogenic role in various malignant tumors, such as gastric cancer and hepatocellular carcinoma. However, the underlying molecular mechanism of ZFAS1 in glioma has not been fully clarified. In this study, we found that the expression of ZFAS1 was upregulated in both glioma tissues and cell lines. Functional experiments revealed that ZFAS1 promoted glioma proliferation, migration and invasion, and increased resistance to temozolomide in vitro. By using online databases, RNA pull-down assays and luciferase reporter assays, ZFAS1 was demonstrated to act as a sponge of miR-150-5p. Furthermore, proteolipid protein 2 (PLP2) was shown to be the functional target of miR-150-5p. Rescue experiments revealed that ZFAS1 regulated the expression of PLP2 by sponging miR-150-5p. Finally, a xenograft tumor assay demonstrated that ZFAS1 promoted glioma growth in vivo. Our results showed that ZFAS1 promoted glioma malignant progression by regulating the miR-150-5p/PLP2 axis, which may provide a potential therapeutic target for the treatment of glioma.

Long non-coding RNA SNHG5 promotes glioma progression via miR-205/E2F3 axis.

In recent years, many studies have reported on the abnormal expression and correlation of long non-coding RNAs (lncRNAs) in tumours. However, the accurate molecular mechanism of lncRNAs in glioma is still in its infancy. In the present study, we aimed to explore the molecular mechanism of small nucleolar RNA host gene 5 (SNHG5) in glioma progression. First, we found that SNHG5 expression was higher in glioma and was related to glioma glucose uptake, migration and invasion. Second, through a series of assays, we concluded that SNHG5 acts as a sponge for miR-205, which inhibits tumour growth in glioma by targeting E2F transcription factor 3 (E2F3). Third, using a xenograft mouse model, we demonstrated that SNHG5 regulates tumourigenesis in vivo Taken together, our results show that the SNHG5/miR-205/E2F3 axis is involved in glioma progression and may provide a new therapeutic target for the diagnosis and therapy of glioma.

Long non-coding RNA HOTAIR acts as a competing endogenous RNA to promote glioma progression by sponging miR-126-5p.

LncRNA HOX transcript antisense intergenic RNA (HOTAIR) has been shown to play prominent roles in tumorigenesis. However, its precise molecular mechanism in glioma has not been completely elucidated. In this study, we found that HOTAIR was aberrantly up-regulated in glioma tissues and was negatively correlated with miR-126-5p expression. Next, we determined that HOTAIR promote glioma progression by sponging miR-126-5p. Subsequently, glutaminase (GLS) was confirmed to be a direct target of miR-126-5p using bioinformatics software and a luciferase reporter assay. Moreover, HOTAIR could modulate GLS expression by functioning as a competing endogenous RNA (ceRNA) for miR-126-5p. Taken together, our study clarified that the HOTAIR/miR-126/GLS pathway is involved in glioma progression and may potentially serve as a target for glioma therapy.

MiR-520b inhibits the development of glioma by directly targeting MBD2.

MicroRNAs play important roles in the process of cancer, which microRNA-520b (miR-520b) has been reported to play critical roles in tumor progression in many types of cancers. However, its role in glioma remains unknown. In this study, we found that miR-520b could inhibit growth and progression in glioma by targeting methyl-CpG-binding domain 2 (MBD2). First, we analyzed the expression of miR-520b in different glioma grades and different cell lines (U87, U251 and astrocyte). Then we assessed the effect of miR-520b on glucose metabolism, invasion, angiogenesis and chemosensitivity in U87 and U251 cells. By using an online database, miR-520b was found to directly bind to the 3'-untranslated regions (3'-UTR) of MBD2 and reduce its expression at the protein level, which further inhibits the development of glioma. MBD2 was also found to be over-expressed in human glioma tissues and in U87 and U251 cells and its level was inversely correlated with that of miR-520b. Furthermore, restoration of MBD2 partially rescued the miR-520b-induced inhibitory effect on glucose metabolism, invasion, angiogenesis and chemosensitivity in glioma cells. In summary, to date, this is the first study to demonstrate that miR-520b functions as a tumor suppressor in glioma by directly targeting MBD2, suggesting that MBD2 may be a potential therapeutic target for glioma.

MiR-421 inhibits the malignant phenotype in glioma by directly targeting MEF2D.

MicroRNA-421 (miRNA-421) dysregulation has been found in various human tumors, however, the biological function and molecular mechanism of miR-421 in glioma remain unclear. In this study, we investigated the potential biological roles of miR-421 in glioma cell lines. First, we demonstrated that compared with that of low grade gliomas (LGG), miR-421 expression is much lower in high grade gliomas (HGG) within the CGGA (Chinese Glioma Genome Atlas) database. MiR-421 expression in 5 normal brain tissues and 20 glioma tissues were in agreement with the result in the CGGA. Second, exogenous expression of miR-421 inhibited glucose metabolism, invasion, angiogenesis and enhanced the radiosensitivity in glioma cell lines. Third, through an online database, myocyte enhancer factor 2D (MEF2D) was identified as a target of miR-421. Interestingly, down-regulation of MEF2D led to an inhibitory effect on glioma glucose metabolism, invasion, angiogenesis and enhancing effect on radiosensitivity, which was similar to the effects of the up-regulation of miR-421. Simultaneously, overexpression of MEF2D partially restored the effect of miR-421 on the glioma cell lines. Finally, in a xenograft model, overexpression of miR-421 suppressed tumorigenicity. These data collectively suggested miR-421 may suppress tumor-associated activity in gliomas by targeting MEF2D.

Recombinant osteopontin attenuates experimental cerebral vasospasm following subarachnoid hemorrhage in rats through an anti-apoptotic mechanism.

Cerebral vasospasm (CVS) is an important pathological process following subarachnoid hemorrhage (SAH). Osteopontin (OPN), a pleiotropic extracellular glycoprotein, has been reported to be able to induce MKP-1 in the spastic cerebral arteries and prevent vasospasm after SAH. The purpose of this study was to investigate the protective effects of recombinant OPN (r-OPN) on CVS following SAH and the underlying mechanisms associated with its anti-apoptotic effect. Eighty male Sprague Dawley rats (weighing 300-375g) were randomly assigned to four groups: (1) sham+vehicle (n=20), (2) SAH+vehicle (n=20), (3) SAH+OPN0.03 (0.03µg) (n=20), (4) SAH+OPN0.1 (0.1µg) (n=20). The double injection model of cisterna magna was performed on day 0 and 48h after the first induction. r-OPN was administered intraventricularly nearly 30min after the first SAH. After neurological score assessment, rats were sacrificed 72h after the first SAH. The cross-sectional area and thickness of basilar arteries (BA) were measured under Hematoxylin-eosin (H&E) staining. Endothelial cell apoptosis was identified by terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining. Immunohistochemistry was used to assess the expression of p-Akt and cleaved caspase-3 in BA. Western blot analysis was applied to evaluate the expression of p-Akt, cleaved caspase-3, Bax and Bcl-2 in BA. r-OPN improved neurological scores and attenuated vasospasm. r-OPN significantly reduced expression of cleaved caspase-3 and Bax in BA following SAH, and increased the level of p-Akt and Bcl-2, coupled with reduced apoptosis of endothelial cell in BA. These results demonstrate that r-OPN can attenuate vasospasm after SAH through a suppressed apoptotic response, which may provide a novel therapeutic target for cerebral vasospasm.

[Management of ruptured aneurysm of anterior communicating artery by emergency operation].

OBJECTIVE: To investigate the effectiveness of emergency operation on ruptured anterior communicating artery. METHODS: Twenty-one cases of ruptured anterior communicating aneurysms, 9 of grade III, 10 of grade IV and 2 grade V according to Hunt-Hess classification, were treated by emergency clipping. RESULTS: By the time of being discharged from hospital, 16 patients were perfectly recovered, 2 suffered from moderated disability, 1 suffered from severe disability and 2 were dead. No patients of grade III before operation died. CONCLUSION: Emergency clipping of ruptured aneurysm of anterior communicating artery prevents death and deterioration of condition caused by aneurysmal re-rupture and relieves the secondary cerebral vasospasm, thus decreasing the mortality and improving the prognosis.