Identification of miR­25­3p as a tumor biomarker: Regulation of cellular functions via TOB1 in breast cancer.

Breast cancer is the most common cancer in women and is one of the three most common malignancies worldwide. Serum microRNAs (miRNAs/miRs) are ideal biomarkers for tumor diagnosis and prognosis due to their specific biological characteristics. In several different types of cancer, miRNAs are associated with cell migration and invasion. In the present study, miR­25­3p expression levels were detected in tissue and serum samples derived from patients with breast cancer, and the diagnostic and prognostic value of miR­25­3p in breast cancer was evaluated. Cellular function assays were performed to evaluate the role of miR­25­3p in breast cancer. Moreover, dual­luciferase reporter assays and western blotting were performed to investigate the target of miR­25­3p. miR­25­3p expression was upregulated in breast cancer tissue and serum samples compared with normal breast tissue and serum samples. Patients with breast cancer with high serum miR­25­3p levels were more likely to have lymph node metastasis compared with those with low serum miR­25­3p levels. The area under the curve for miR­25­3p in the diagnosis of breast cancer was 0.748, with 57.1% sensitivity and 95.0% specificity. Moreover, the Kaplan­Meier survival curves demonstrated that patients with breast cancer with a low expression of serum miR­25­3p had a higher overall survival rate compared with patients with a high serum miR­25­3p expression. miR­25­3p knockdown suppressed breast cancer cell proliferation and invasion, and transducer of ERBB2, 1 (TOB1) was identified as a potential target gene regulated by miR­25­3p. Therefore, the present study suggested that miR­25­3p regulated cellular functions via TOB1 in breast cancer; therefore, miR­25­3p may serve as a breast cancer biomarker.

Exercise prevents raphe nucleus mitochondrial overactivity in a rat depression model.

Monoamine deficit and mitochondrial dysfunction may underlie depression. Serotoninergic neurons from raphe nuclei project widely and may be involved in depression. This study used chronic unpredictable stress (CUS) in rats as a model of depression to assess the effects of CUS, exercise and fluoxetine on mitochondrial function and serotonin levels in the raphe nuclei. Rats were divided into 4 groups (6 per group): control (C); depression (D), CUS for 28days; depression+exercise (DE), treadmill exercises from days 11-28 of CUS; depression+fluoxetine (DF), fluoxetine (5mg/kg/d i.g.) from days 11 to 28 of CUS. Behavioral changes were assessed using body weight, sucrose consumption tests (anhedonia) and open field tests (locomotor/exploratory behavior). Raphe nucleus mitochondrial function was determined using the respiratory control ratio, ATP synthesis rate, and activities of superoxide dismutase and glutathione peroxidase. Serotonin levels were measured in the raphe nuclei and hippocampus. On day 28 of CUS, body weight was higher in group C than in groups D, DE and DF (P<0.001), and higher in group DE than in group D or DF (P<0.05). Sucrose consumption was higher in group C than in groups D, DE and DF (P<0.001), higher in group DE than in groups D (P<0.001) or DF (P<0.05), and higher in group DF than in group D (P<0.05). All measures of mitochondrial function were increased in group D compared with the other groups (P<0.01). Hippocampal serotonin was lower in group D than in the other groups (P<0.01); levels in the raphe nuclei were elevated in group DE compared with the remaining groups (P<0.001). CUS in rats may cause overactivation of the mitochondria in the raphe nuclei, and exercise training may suppress these changes.