BackgroundThe polyphenol resveratrol (Rev) has been reported to exhibit cardioprotective effects, such as inhibition of TAC (transverse aortic constriction) or isoprenaline (ISO)‐induced hypertrophy. MicroRNA‐155 (miR‐155) was found to be decreased in hypertrophic myocardium, which could be further reduced by pretreatment of Rev. The study was designed to investigate the molecular effects of miR‐155 on cardiac hypertrophy, focusing on the role of breast cancer type 1 susceptibility protein (BRCA1).Methods and ResultsWe demonstrated that Rev alleviated severity of hypertrophic myocardium in a mice model of cardiac hypertrophy by TAC treatment. Down‐regulation of miR‐155 was observed in pressure overload– or ISO‐induced hypertrophic cardiomyoctyes. Interestingly, administration of Rev substantially attenuated miR‐155 level in cardiomyocytes. In agreement with its miR‐155 reducing effect, Rev relieved cardiac hypertrophy and restored cardiac function by activation of BRCA1 in cardiomyoctyes. Our results further revealed that forkhead box O3a (FoxO3a) was a miR‐155 target in the heart. And miR‐155 directly repressed FoxO3a, whose expression was mitigated in miR‐155 agomir and mimic treatment in vivo and in vitro.ConclusionsWe conclude that BRCA1 inactivation can increase expression of miR‐155, contributing to cardiac hypertrophy. And Rev produces their beneficial effects partially by down‐regulating miR‐155 expression, which might be a novel strategy for treatment of cardiac hypertrophy.

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OBJECTIVETo study the expression of phosphorylated p38 mitogen-activated protein kinase (p-p38) and uPA and the correlation of their expression with breast cancer clinicopathological characteristics, and to investigate the role of the p38MAPK-signaling pathway in regulating uPA expression in breast cancer cells. METHODS Immunohistochemistry (S-P) was used to test the expression of p-p38 and uPA in 60 specimens of breast cancer tissues. Western blots were adopted to detect expression of the p-p38 and uPA proteins in MDA-MB-231 and MCF-7 breast cancer cells, and uPA expression aĞ er treatment with SB203580, a specię c inhibitor of p38 MAPK. RESULTSThe positive rate of the p-p38 protein and uPA protein expression in the breast cancer tissues was 56.7% and 60.0%,respectively. The expression of p-p38 was positively related to the expression of uPA (r = 0.316, P < 0.05). The expression of p-p38 and uPA was related to lymph node metastasis and the TNM stage (P < 0.05), but it was not related to the patient's age or tumor size (P > 0.05). The expression of p-p38 and uPA in MDA-MB-231 cells was higher than that in MCF-7 cells. SB203580 inhibited the p38 MAPK pathway and reduced uPA protein expression. CONCLUSION The p38 MAPK-signaling pathway promotes breast cancer malignant progression by up-regulating uPA expression ,and it may be an important process in breast cancer invasion and metastasis.KEY WORDS: p38 MAP kinase, uPA, breast cancer.

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