Novel, non-invasive biomarkers with high sensitivity and specificity are critical for breast cancer treatment, and prognosis. MicroRNA (miR)-96 has been demonstrated to be highly expressed in several solid malignancies, including breast cancer. However, its expression and function in the metastasis and prognosis of breast cancer have not been fully explored, and its regulation mechanisms remain unclear. In the present study, the serum miR-96 expression in healthy controls, benign and malignant breast cancer types was compared by using reverse transcription-quantitative polymerase chain reaction. The effect of chemotherapy on miR-96 expression in breast cancer was also investigated. Result revealed that miR-96 expression was increased in malignant breast cancer types and reduced in patients following chemotherapy treatment. The effect of miR-96 manipulation on the migration of breast cancer cells was also investigated by using wound healing, and Transwell migration assays. These results revealed that the induced expression of miR96 led to enhanced wound closing and trans-membrane cell numbers. By using bioinformatics analysis, western blotting and immunohistochemical staining, the metastasis suppressor-1 (MTSS1) gene was identified to be the functional target of miR-96 in the promotion of cell migration. In conclusion, it was identified that miR-96 exhibited an increased level in serum samples of patients with malignant breast cancer in comparison with benign breast tumor types and health controls and may be substantially reduced by chemotherapy treatment, implying that it may be used as a prognostic marker in breast cancer. miR-96 overexpression may inhibit migration of breast cancer cells by downregulating MTSS1 expression.
Visit-to-visit variability of glycated hemoglobin (HbA1c) is a marker of long-term glycemic fluctuation, which has been related to increased risk of macrovascular complications in patients with type 2 diabetes mellitus (T2DM). The association between HbA1c variability and retinopathy in patients with T2DM, however, has been inconsistent in previous studies. In order to fully evaluate the above association, we conducted a meta-analysis. Observational studies related to the aim of the meta-analysis were identified by search of PubMed, Web of Science, and Embase databases. Studies with HbA1c variability evaluated as the standard deviation (SD) and/or the coefficients of variation (CV) of HbA1c were included. The results were analyzed using a random-effects model that incorporated potential heterogeneity between studies. Twelve observational studies involving 44 662 T2DM patients contributed to the meta-analysis. Overall, 5150 (11.5%) patients developed retinopathy. Pooled results showed that compared to patients with lower HbA1c variability, T2DM patients with higher HbA1c-SD (relative risk [RR]: 1.48, 95% confidence interval [CI]: 1.24 to 1.78, p<0.001, I2=34%) and higher HbA1c-CV (RR: 1.29, 95% CI: 1.05 to 1.59, p=0.02, I2=0%) were both associated with higher risk of DR. For studies with HbA1c-SD, the association was not significantly affected by study characteristics such as country, study design, mean age, disease duration, adjustment of mean HbA1c, or quality scores (p for subgroup difference all>0.05). In conclusion, higher HbA1c variability may be associated with an increased risk of retinopathy in patients with T2DM.
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