No abstract

MicroRNA 181a (miR-181a) was found dysregulated in a variety of human cancers and significantly associated with clinical outcome of cancer patients. However, the direct role of miR-181a has not yet been characterized in osteosarcoma progression. This study was aimed at investigating the effects of miR-181a on osteosarcoma cell biological behavior. First, the expression of miR-181a in osteosarcoma cell lines (MG63, HOS, SaOS-2, and U2OS) and a human osteoblastic cell line (hFOB1.19) was detected by qRT-PCR. Results showed that miR-181a was overexpressed in osteosarcoma cell lines compared to human osteoblastic cell line (hFOB1.19). To investigate the effects of miR-181a on proliferation, apoptosis, and invasion of osteosarcoma cells, we generated human osteosarcoma MG63 cells in which miR-181a was either overexpressed or depleted. The MG63 cell viability, cycle, apoptosis, and invasive ability were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide staining, propidium iodide (PI) staining, Annexin V-FITC/PI double staining, and Transwell invasion experiment, respectively. The results showed that MG63 cell viability, proliferation, and invasive abilities were suppressed, and the apoptosis was enhanced in the group with underexpression of miR-181a. The viability, proliferation, and invasive abilities were improved, and the apoptosis was inhibited in the group with overexpression of miR-181a. The results from Western blotting indicated that miR-181a might be associated with the up-regulation of bcl-2 and matrix metalloproteinase 9 and the down-regulation of tissue inhibitor of metalloproteinases-3 and p21 in MG63 cells. Taken together, our results suggested that miR-181a might facilitate proliferation and invasion and suppress apoptosis of osteosarcoma cells, which might be a potential target for the treatment of osteosarcoma.

ObjectiveTo determine whether educational level and overweight/obesity was associated with the development of diabetes among Chinese adult men and women.MethodsA cohort (2000–2011) of 10 704 participants aged 18–59 years (8 238 men, 2 466 women) in Qingdao Port Health Study (QPHS) were recruited in this study. The personal lifestyle, height, weight, waist circumference, resting heart rate, blood pressure, fasting blood glucose, total cholesterol, triglycerides and plasma uric acid were collected annually in a comprehensive health checkup program. Cox proportional hazards regression models were used to estimate the association of factors and incidence of diabetes.ResultsDuring 110 825 person-years of follow-up, 1 056 new onset cases (9.5 per 1 000 person-years) of diabetes were identified. With normal weight as reference, the multiple-adjusted hazard ratio (HR) (95%CI) of diabetes was 1.69(1.38–2.09) for overweight and 2.24(1.66–3.02) for obesity among men, which was 1.81(1.12–2.92) and 2.58(1.37–4.86) among women, respectively. Compared with the participants with high educational level, those with low educational level had a higher risk of diabetes (multiple-adjusted HR (95%CI): 1.43(1.11–1.86)) among men. The association was not found among women and the adjusted HR (95%CI) of diabetes was 1.56(0.89–2.76). The increased risks of low educational level were independent of mediators among men, through normal weight (P for trend = 0.0313) and overweight (P for trend = 0.0212) group but not obesity group (P for trend = 0.0957).ConclusionBaseline overweight/obesity was an independent risk factor for diabetes for both men and women. Low educational level was adversely associated with incidence of diabetes through normal weight, overweight and obesity groups, with the association being substantially attenuated by mediating factors only in the obesity group among men. The association was not found among women.

Glioma is one of the most common type of primary intracranial tumor. Although great advances have been achieved in treatment of glioma, the underlying molecular mechanisms remain largely unknown. Previous studies demonstrated that FBP1 is a transcriptional regulator of c-Myc and acts as an important prognostic indicator in many cancers. Our study aimed to assess the expression and function of FBP1 in human glioma. Immunohistochemical and Western blot analysis were performed in human glioma and normal brain tissues. High FBP1 expression (located in cell nuclei) was observed in 70 samples and its level was correlated with the grade of malignancy. A strongly positive correlation was observed between FBP1 and c-Myc (P = 0.005) and Ki-67 expression (P = 0.009). In a multivariate analysis, high FBP1 and c-Myc expressions were showed to be associated with poor prognosis in glioma. While in vitro, following serum stimulation of starved U87MG cells, the expression of FBP1 was upregulated, as well as c-Myc and PCNA. Moreover, knockdown of FBP1 by siRNA transfection diminished the expression of c-Myc and arrested cell growth at G1 phase. Collectively, our results shows that the expression of FBP1 is in close correlation with c-Myc level and cell proliferation in glioma and provides a potential strategy to develop FBP1 inhibitors as novel anti-tumor agents.

Overexpression of C-terminal binding protein-2 (CtBP2) has been noted to correlate with cancer metastasis in several human cancers including breast cancer. The aim of this study was to examine the effect of cyclase-associated protein 1 (CAP1) overexpression on CtBP2 expression and related mechanism in the metastasis of breast cancer. Immunohistochemical analysis was performed in 100 human breast carcinoma samples, and the data were correlated with clinicopathologic features. Furthermore, Western blot analysis was performed for CAP1 and CtBP2 in breast carcinoma samples and cell lines to evaluate their protein levels and molecular interaction. We found that the expression of CAP1 was positively related to CtBP2 expression (P<0.01); moreover, CAP1 expression was significantly correlated with histologic grade (P<0.01) and negatively related to E-cadherin expression (P<0.01). Meanwhile, CtBP2 expression obtained similar results. Kaplan-Meier survival analysis showed that overexpression of CAP1 and CtBP2 exhibited a significant correlation with poor prognosis in human breast cancer (P<0.01). While in vitro, we employed siRNA technique to knockdown CAP1 and CtBP2 expressions and observed their effects on MDA-MB-231 cells growth. CtBP2 depletion by siRNA-inhibited cell proliferation, resulted in increased E-cadherin levels. Moreover, knockdown of CAP1 resulted in decreased CtBP2 and increased E-cadherin expression. On the basis of these results, we suggested that CAP1's oncogenic abilities appear to be triggered at least in part by the modulation of CtBP2 and E-cadherin, which might serve as a future target for breast cancer.