MicroRNA-96 (miR-96) is transcriptionally associated with the induction of chemoresistance following chemotherapy by targeting to FOXO1 mRNA at one of two predicted binding sites in its 3'-untranslated region sequence. The upregulation of miR-96 is associated with a high risk of chemoresistance. Nevertheless, the mechanism by which miR-96 is upregulated remains largely undefined. In the present study, the gastric cancer SGC7901 cell line was treated with different doses of the chemotherapeutic agents cisplatin and doxorubicin. miR-96 expression was analyzed by reverse transcription-quantitative polymerase chain reaction at different time points. Western blot and chromatin immunoprecipitation were performed to analyze the expression levels of the target gene. The effects of miR-96 on chemosensitivity were assessed by a carboxyfluorescein succinimidyl ester/propidium iodide labeling assay, and its effects on proliferation were assessed by Cell Counting Kit-8 or EdU staining assays. The results demonstrated that treatment with a low dose of either chemotherapeutic agent induced miR-96 expression. Upregulation of miR-96 caused the post-transcriptional repression of FOXO1 expression. Decreases in FOXO1 protein levels led to a decrease in the transcriptional activity of the cyclin-dependent kinase inhibitor 1A (CDKN1A, also known as p21) promoter region, and thus the expression of p21 was downregulated in a tumor protein p53-independent manner. As a result, induction of miR-96 expression caused chemoresistance and promoted proliferation in SGC7901 cells. Taken together, the results of the present study revealed that treatment with cisplatin or doxorubicin could induce expression of miR-96 at certain doses. Upregulation of miR-96 is partially associated with chemoresistance and miR-96 can also promote cell proliferation by repressing p21.

Fermented milk supplemented with two probiotic strains (Bifidobacterium lactis Bi-07 and Lactobacillus acidophilus NCFM) and a prebiotic (isomaltooligosaccharide) was orally administered to Wistar rats for 30 days using three dosages. A commercial yogurt was used as a placebo. After treatment, the total protein, hemoglobin, and albumin levels in serum were significantly increased in female rats compared with those in the control group (p<0.05), whereas no significant change occurred in the male rats. A significant decrease in serum glucose levels was observed in male rats administered a low dosage of the tested fermented milk (p<0.05). The serum triglyceride level was significantly decreased in both male and female rats (p<0.05). No significant differences were found between rats groups in body weight, food intake, food utilization rate, red blood cell counts, white blood cell counts, alanine aminotransferase, aspartate aminotransferase, urea nitrogen, creatinine, and total cholesterol. These results suggest that the fermented milk supplemented with synbiotics altered the nutritive status of the host animal and contributed to their health. However, such potent health-promoting effects could be deeply associated with the dose and sex specific. Therefore, different physiological targets and population characteristics should be managed with different combinations of probiotics and prebiotics.