Osteosarcoma is a common, high-risk primary bone malignancy that mostly affects the younger population. There has been no marked improvement in the clinical outcomes of osteosarcoma patients to date, and cancer recurrence and metastasis are common in high-grade osteosarcoma. Therefore, identifying new biomarkers and novel therapeutic targets is crucial for improving the prognosis of osteosarcoma patients. In the present study, the MG63 human osteosarcoma cell line was employed to examine the role of microRNA (miR)-15a in regulating cellular activities under hypoxic conditions. It was demonstrated that hypoxia stimulates migration and invasion in MG63 cells, which was correlated with the downregulation of miR-15a and upregulation of B-cell lymphoma 2 (Bcl-2) expression. Introduction of miR-15a or knockdown of endogenous Bcl-2 may reduce hypoxia-induced cell invasion and migration through the regulation of matrix metalloproteinases. Analysis of the expression of miR-15a indicated that hypoxia repressed the transcription of deleted in lymphocytic leukemia 2 (DLEU2), which is the host gene of miR-15a. These findings indicated that miR-15a may be a valuable target for the treatment of osteosarcoma, particularly for patients with high-grade cancer or heavy tumor burden.

The present study aimed to identify novel intervertebral disc degeneration (IDD)-associated long noncoding (lnc)RNAs and genes. The lncRNA and mRNA microarray dataset GSE56081 was downloaded from the Gene Expression Omnibus database and included 5 samples from patients with degenerative lumbar nucleus pulposus and 5 normal controls. Differentially expressed lncRNAs or differentially expressed genes (DEGs) were identified and co-expression network analysis was performed followed by functional analysis for genes in the network. Additionally, a microRNA (miRNA)-lncRNA-mRNA competing endogenous RNA (ceRNA) regulatory network was constructed based on DEGs and lncRNAs in the co-expression network. Furthermore, a literature search was performed to identify specific miRNAs that had been previously associated with IDD and a specific miRNA-associated ceRNA network was extracted from the co-expression network. A total of 967 genes and 137 lncRNAs were differentially expressed between IDD samples and controls. A co-expression network was constructed and contained 39 differentially expressed lncRNAs and 209 DEGs, which were primarily involved in ‘skeletal system development’, ‘response to mechanical stimulus’ and ‘bone development’. Furthermore, a ceRNA network was established, including 79 miRNAs, 9 downregulated lncRNAs and 148 DEGs. The identified miRNAs included a previously reported disease-associated miRNA, hsa-miR-140. The present study demonstrated that hsa-miR-140 was regulated by three lncRNAs in the hsa-miR-140-associated ceRNA network, including KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1), OIP5 antisense RNA 1 (OIP5-AS1) and UGDH antisense RNA 1 (UGDH-AS1). KCNQ1OT1 was co-expressed with neurochondrin (NCDN) and lon peptidase 2, peroxisomal. In addition, the lncRNAs OIP5-AS1 and UGDH-AS1 targeted several overlapping co-expressed genes, including forkhead box F1 (FOXF1) and polycystin 1, transient receptor potential channel interacting (PKD1). Therefore, KCNQ1OT1 may regulate the expression of NCDN, and OIP5-AS1 and UGDH-AS1 may affect the expression of FOXF1 and PKD1 in IDD. Further experiments are required to validate the results of the present study, which may provide valuable insights into the identification of novel biomarkers associated with IDD.

Background/Aims: Mechanical load can regulate disc nucleus pulposus (NP) biology in terms of cell viability, matrix homeostasis and cell phenotype. N-cadherin (N-CDH) is a molecular marker of NP cells. This study investigated the role of N-CDH in maintaining NP cell phenotype, NP matrix synthesis and NP cell viability under high-magnitude compression. Methods: Rat NP cells seeded on scaffolds were perfusion-cultured using a self-developed perfusion bioreactor for 5 days. NP cell biology in terms of cell apoptosis, matrix biosynthesis and cell phenotype was studied after the cells were subjected to different compressive magnitudes (low- and high-magnitudes: 2% and 20% compressive deformation, respectively). Non-loaded NP cells were used as controls. Lentivirus-mediated N-CDH overexpression was used to further investigate the role of N-CDH under high-magnitude compression. Results: The 20% deformation compression condition significantly decreased N-CDH expression compared with the 2% deformation compression and control conditions. Meanwhile, 20% deformation compression increased the number of apoptotic NP cells, up-regulated the expression of Bax and cleaved-caspase-3 and down-regulated the expression of Bcl-2, matrix macromolecules (aggrecan and collagen II) and NP cell markers (glypican-3, CAXII and keratin-19) compared with 2% deformation compression. Additionally, N-CDH overexpression attenuated the effects of 20% deformation compression on NP cell biology in relation to the designated parameters. Conclusion: N-CDH helps to restore the cell viability, matrix biosynthesis and cellular phenotype of NP cells under high-magnitude compression.

Hepatoma-derived growth factor (HDGF) is a novel jack-of-all-trades in cancer. Here we quantify the prognostic impact of this biomarker and assess how consistent is its expression in solid tumors. A comprehensive search strategy was used to search relevant literature updated on October 3, 2014 in PubMed, EMBASE and WEB of Science. Correlations between HDGF expression and clinicopathological features or cancer prognosis was analyzed. All pooled HRs or ORs were derived from random-effects models. Twenty-six studies, primarily in Eastern Asia, covering 2,803 patients were included in the analysis, all of them published during the past decade. We found that HDGF overexpression was significantly associated with overall survival (

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