To reveal the potential molecular mechanism of glioblastoma multiforme (GBM) and provide the candidate biomarkers for GBM gene therapy. Microarray dataset GSE50161 was obtained from GEO database. The differentially expressed genes (DEGs) were identified between GBM samples and control samples, followed by the module partition analysis based on WGCNA. Then, the pathway and functional enrichment analyses of DEGs were performed. The hub genes were further investigated, followed by the survival analysis and data validation. A total of 1913 DEGs were investigated between two groups, followed by analysis of 5 modules using WGCNA. These DEGs were mainly enriched in functions like inflammatory response. The hub genes including upregulated N-Myc and STAT Interactor (NMI), Capping Actin Protein-Gelsolin Like (CAPG), and Proteasome Subunit Beta 8 (PSMB8) were revealed as potential liquid biopsy molecules for GBM diagnose. Moreover, Nucleolar and Spindle Associated Protein 1 (NUSAP1) and G Protein-Coupled Receptor 65 (GPR65) were outstanding genes in survival analysis. Our results suggested that CPNE6, HAPLN2, CMTM3, NMI, CAPG, and PSMB8 might be used as potential molecules for liquid biopsy of GBM. NUSAP1 and GPR65 might be novel prognostic targets for GBM gene therapy. Furthermore, the upregulated NMI might play an important role in GBM progression via inflammatory response.

Background/Aims: LncRNA GAS5, a growth suppressor, has been reported to exert anti-tumor actions in various cancers, whereas the exact mechanism underling the anti-tumor action is still unclear. This study was aimed to investigate the effect of lncRNA GAS5 on osteosarcoma and tried to decode the underling mechanisms. Methods: Expressions of lncRNA GAS5 in MG-63 cells were silenced by shRNA transfection, while were overexpressed by vector transfection. Cell viability, migration, invasion and apoptosis were respectively assessed by MTT, Transwell assay and flow cytometry. Regulations between lncRNA GAS5 and miR-203a, as well as between miR-203a and TIMP2 were detected by qPCR, western blot and dual luciferase activity assay. Results: LncRNA GAS5 was down-regulated in MG-63 and OS-732 cells compared to hFOB1.19 cells. Silence of lncRNA GAS5 significantly promoted MG-63 cells viability, migration and invasion, and up-regulated Cyclin D1, Cyclin B1, CDK1 and CDK4 expressions. miR-203a was negatively regulated by lncRNA GAS5. The promoting activities of lncRNA GAS5 silence on MG-63 cells growth and metastasis were reversed by miR-203a suppression. TIMP2 was a target of miR-203a and the anti-growth and anti-metastasis actions of miR-203a suppression were reversed by TIMP2 silence. Further, lncRNA GAS5 silence, miR-203a overexpression, and TIMP2 silence could activate PI3K/AKT/GSK3β signaling while block NF-κB signaling. Conclusion: LncRNA GAS5 might be a tumor suppressor in osteosarcoma via sponging miR-203a, sequestering miR-203a away from TIMP2.

Osteosarcoma is a rare malignant bone tumor with high degree of malignancy. HULC (highly upregulated in liver cancer), a long noncoding RNA (lncRNA) was involved in hepatocellular carcinoma development and progression, but its underlying mechanism in osteosarcoma is unknown. The aim of this study was to explore the functional role of HULC in osteosarcoma. The study was conducted in human osteosarcoma cell lines and the expression of HULC in the cell lines was detected by qRT-PCR. Furthermore, the effects of HULC on tumorigenicity of osteosarcoma cells were evaluated by in vitro assays. Results revealed that HULC was highly expressed in osteosarcoma MG63and OS-732 cells compared to osteoblast hFOB1.19 cells. Suppression of HULC in osteosarcoma cells inhibited cell viability, migration, invasion, and promoted apoptosis. HULC functioned as an endogenous sponge for miR-122, and its silence functioned through upregulating miR-122. HNF4G was a target of miR-122, and the effect of HNF4G on OS-732 cells was the same as HULC. Furthermore, overexpression of miR-122 inactivated PI3K/AKT, JAK/STAT, and Notch pathways by downregulation of HNF4G. These findings suggest that knockdown of HULC inhibited proliferation, migration, and invasion by sponging miR-122 in osteosarcoma cells. HULC may act as a novel therapeutic target for management of osteosarcoma.