The potential value of lncRNA-BC050642 in osteosarcoma origination and outcomes.

Background: The purpose of our research was to explore potential value of lncRNA-BC050642 in osteosarcoma origination and prognosis. Methods: In this study, the tissue specimens were collected from 97 osteosarcoma patients and 97 age-matched healthy controls. Besides, human osteosarcoma cell lines U2OS and normal osteoblastic cell line hFOB1.19 were selected for experiments in vitro. lncRNA-BC050642 levels were measured through quantitative real-time polymerase chain reaction (qRT-PCR). Relative expression of the gene c-myc was determined via ELISA analysis. x2 test was implemented to appraise possible relationship between BC050642 level and clinicopathological features. Cell proliferation assay, plate colony formation assay, and cell apoptosis assay were adopted to analyze the influence of BC050642 on tumor development. Besides, prognostic value of BC050642 was estimated using Kaplan-Meier and cox regression analysis. Results: BC050642 levels showed distinctive increases in osteosarcoma tissues and cell lines compared with controls. And c-myc expression was down-regulated in osteosarcoma. There was a negative correlation between the expressions of BC050642 and c-myc. BC050642 expression was proved to be significantly correlated with Ennking and histological type. Up-regulated BC050642 could promote cell proliferation, induce colony formation and meanwhile inhibit cell apoptosis. Conclusions: BC050642 is up-regulated in osteosarcma and its over-expression promotes tumor development via down-regulating the expression of c-myc. It also may be an independent prognostic biomarker for osteosarcoma.

The association of genetic variants in FGFR2 with osteoporosis susceptibility in Chinese Han population.

Objective: The present study was conducted for exploring the influence of fibroblast growth factor 2 receptor (FGFR2) gene polymorphisms on osteoporosis occurrence risk in the Chinese population.Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was conducted for the genotyping of polymorphism in 145 osteoporosis patients and 123 controls. The status of Hardy-Weinberg equilibrium was detected in the control group. Genotype and allele frequency comparison of polymorphism between the two groups was performed by χ2 test, odds ratio (OR) with 95% confidence interval (95% CI) was used for the result expression about the association of FGFR2 polymorphisms with osteoporosis. Furthermore, the results were adjusted by clinical features via logistic regression analysis.Results: AA genotype and A allele of rs2420946 were significantly associated with the increased risk of osteoporosis development adjusted by clinical features (OR = 2.238, 95% CI = 1.055-4.746; OR = 1.482, 95% CI = 1.042-2.019). Similarly, CC genotype and C allele frequencies of rs1219648 were detected the significant difference between the case and control groups (P<0.01); moreover, it was still significant by the adjustion of clinical features, which indicated that rs1219648 was significantly associated with the risk of osteoporosis occurrence (OR = 2.900, 95% CI = 1.341-6.271; OR = 1.602, 95% CI = 1.126-2.279). Haplotype T-A-C-T also obviously increased the occurrence risk of osteoporosis (OR = 1.844, 95% CI = 1.180-2.884). Besides, the significant interaction of FGFR2 polymorphisms with drinking status in osteoporosis was also found (P<0.05), especially rs2981579.Conclusion:FGFR2 rs2420946 and rs1219648 polymorphisms may be the risk factor of osteoporosis in Chinese population. Furthermore, the interaction of FGFR2 polymorphisms with drinking may play an important role in osteoporosis etiology.

Down-regulation of GCLC is involved in microcystin-LR-induced malignant transformation of human liver cells.

Microcystin-LR (MCLR) is a potent hepatotoxin which could lead to the development of hepatocellular carcinoma. However, the mechanisms of its carcinogenic action remain obscure. The catalytic subunit of glutamylcysteine ligase (GCLC) primarily regulates de novo synthesis of glutathione and is central to the antioxidant capacity of the cell, but emerging data suggest that the GCLC expression is associated with cancer development. The purpose of this study was to investigate the role and molecular mechanisms of GCLC in MCLR-induced malignant transformation of a human liver cell line WRL68. During MCLR-induced cell transformation, the expression of GCLC and activity of glutamate-cysteine ligase (GCL) decreased continuously, accompanied with consistent low levels of glutathione (GSH) but high levels of oxidative DNA damages. Furthermore, MCLR markedly inhibited protein phosphatase 2 A (PP2 A), and increased the level of GCLC phosphorylation. In contrast, overexpression of GCLC significantly enhanced the levels of GSH, inhibited oxidative DNA damages, and suppressed MCLR-induced cell invasion and migration, as well as tumor growth in nude mice. GCLC overexpression partially attenuated MCLR-induced PP2 A inhibition. Together, the current results suggest that down-regulation of GCLC is involved in MCLR-induced malignant transformation of human liver cells by inducing oxidative stress.