Glioblastoma multiforme (GBM) is the most common type of primary brain tumour in adults, and presents a very low survival rate. Isocitrate dehydrogenase (IDH)1/2 mutations have been found in ~12% of glioblastomas and are associated with long-term GBM survival. However, the risk factors that influence the prognosis of IDH-wild type GBM remain unclear. Hypoxia-inducible factor (HIF)-1α, an important oxygen-regulated transcription factor, has been demonstrated to serve a crucial role in tumour development and to be associated with a poor prognosis. In addition, caveolin-1 (CAV1) is a plasma membrane organizing protein, the expression of which can also be regulated by a hypoxic microenvironment. The present study therefore aimed to examine the expression levels of HIF-1α and CAV1, and their association with GBM prognosis. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to analyse the expression levels of HIF-1α and CAV1 in paired GBM tumour and adjacent non-tumour tissues. Immunohistochemistry was used to analyse the expression of the two proteins in paraffin-embedded tissues obtained from 42 patients with IDH-wild type GBM. Statistical analyses were performed to examine the correlation between HIF-1α and CAV1 expression and patient prognosis. The results revealed hat the expression levels of HIF-1α and CAV1 were upregulated in IDH-wild type GBM tissues compared to their paired non-tumour tissues (P<0.001). The expression of CAV1 was significantly correlated with high HIF-1α expression (P<0.01). In addition, overexpression of HIF-1α and CAV1 was markedly associated with a poor prognosis (P<0.001). In conclusion, HIF-1α and CAV1 may represent potential biomarkers for IDH-wild type GBM prognosis and potential targets for the development of therapies extending GBM survival.

Background Osteosarcoma (OS) is the most common primary malignancy of bone with a high incidence in children. Circular RNAs (circRNAs) play crucial roles in the carcinogenesis and chemoresistance of OS. In the current work, we focused on the function and mechanism of hsa_circ_0003496 (circ_0003496) in OS progression and chemoresistance. Materials and Methods The expression levels of circ_0003496, miR-370 and Krüppel-like factor 12 (KLF12) mRNA were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The Cell Counting Kit-8 (CCK-8) assay was used to assess the 50% inhibitory concentration (IC50) value and cell proliferation. Cell migration, invasion and apoptosis were detected by transwell assay and flow cytometry, respectively. Western blot analysis was performed to assess the protein level. Targeted relationships among circ_0003496, miR-370 and KLF12 were validated by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. Animal studies were carried out to observe the role of circ_0003496 in vivo. Results Our results indicated that circ_0003496 up-regulation was associated with doxorubicin (DXR) resistance of OS. Circ_0003496 knockdown repressed DXR-resistant OS cell proliferation, migration and invasion, and enhanced apoptosis and DXR sensitivity. Circ_0003496 functioned as a sponge of miR-370, and miR-370 mediated the regulatory effect of circ_0003496 depletion on DXR-resistant OS cell progression and DXR sensitivity. KLF12 was a direct target of miR-370, and miR-370 overexpression suppressed cell progression and enhanced DXR sensitivity by KLF12. Moreover, circ_0003496 protected against KLF12 repression through sponging miR-370. Additionally, circ_0003496 knockdown hampered tumor growth and promoted DXR sensitivity in vivo. Conclusion Our present work suggested that the knockdown of circ_0003496 suppressed OS progression and enhanced DXR sensitivity at least partially through modulating KLF12 expression via functioning as a miR-370 sponge, highlighting new opportunities for OS management.

Low dose anesthesia by either TIVA with propofol or sevoflurane-based mixture anesthesia protocol can help the intraoperative spinal cord monitoring to successfully elicit MEP and perform reliable monitoring for patients below 12 years of age.

Circular RNA (circRNA) is related to many human diseases including osteoarthritis (OA). Our research purpose was to show that functional circRNAs have a role in the pathogenesis of OA, while also identifying potential circRNA that bind to miRNA-27b-3p. Microarray analysis was used to evaluate the expression of CircRNA in OA and normal cartilage. The role and functional mechanism of Circ_0000423 up-regulation were detected in OA and verified in vitro and in vivo . RNA transfection, qRT-PCR, Western blot analysis, immunofluorescence, and dual-luciferase assays were used to investigate the interaction between Circ_0000423 and miRNA-27b-3p in vitro . The roles of Circ_0000423 were discussed in vivo . Our results discovered 11 down-regulated circRNAs and 101 up-regulated circRNAs between control and OA tissues, and confirmed that Circ_0000423 an increase significantly in OA tissues by evaluating the different circRNAs expressions. Meanwhile, luciferase analysis confirmed Circ_0000423 can be directly targeted by miRNA-27b-3p and act as a miRNA-27b-3p sponge. Circ_0000423 can influence MMP-13 and collagen II expression by targeting miRNA-27b-3p expression as ceRNA in OA. Furthermore, AAV-shRNA-Circ 0000423 intra-articular injection slows the progression of OA by decreasing articular cartilage destruction and erosion, joint surface fibrosis, osteophyte formation, MMP-13 expression, and increasing collagen II expression in the articular cartilage of ACLT-induced OA mice model. These findings confirmed that the Circ_0000423-miRNA-27b-3p-MMP-13 axis could affect the pathogenesis of OA which might lead to a novel target for diagnostic molecular biological indicators and potential OA treatments.

Circular RNAs (circRNAs) play a key role in regulating the tumorigenesis and development of human cancers, including osteosarcoma (OS). Of note, the molecular mechanism underlying the progression of OS has remained largely unclear. The present study identified that a novel circRNA circEIF4G2 was upregulated in OS tissues and cells. Moreover, we constructed a circEIF4G2-mediated ceRNA network and revealed that circEIF4G2 was involved in regulating multiple cancer pathways, such as the EGFR signaling pathway, the PI3K-Akt signaling pathway, and the ErbB signaling pathway. Loss-of-function assays showed that circEIF4G2 knockdown significantly suppressed OS cell proliferation, migration, and invasion. Mechanically, we found that circEIF4G2 could directly bind to miR-218, and miR-218 mediated the effect of circEIF4G2 knockdown on OS progression. In conclusion, the present study showed that circEIF4G2 could be a potential biomarker for OS.