Inflammation plays an important role in cardiac injuries. Here, we examined the role of miRNA in regulating inflammation and cardiac injury during myocardial infarction. We showed that mir-155 expression was increased in the mouse heart after myocardial infarction. Upregulated mir-155 was primarily presented in macrophages and cardiac fibroblasts of injured hearts, while pri-mir-155 was only expressed in macrophages. mir-155 was also presented in exosomes derived from macrophages, and it can be transferred into cardiac fibroblasts by macrophagederived exosomes. A mir-155 mimic or mir-155 containing exosomes inhibited cardiac fibroblast proliferation by downregulating Son of Sevenless 1 expression and promoted inflammation by decreasing Suppressor of Cytokine Signaling 1 expression. These effects were reversed by the addition of a mir-155 inhibitor. In vivo, mir-155-deficient mice showed a significant reduction of the incidence of cardiac rupture and an improved cardiac function compared with wild-type mice. Moreover, transfusion of wild-type macrophage exosomes to mir-155 À/À mice exacerbated cardiac rupture. Finally, the mir-155-deficient mice exhibited elevated fibroblast proliferation and collagen production, along with reduced cardiac inflammation in injured heart. Taken together, our results demonstrate that activated macrophages secrete mir-155-enriched exosomes and identify macrophagederived mir-155 as a paracrine regulator for fibroblast proliferation and inflammation; thus, a mir-155 inhibitor (i.e., mir-155 antagomir) has the potential to be a therapeutic agent for reducing acute myocardial-infarction-related adverse events.

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The CDGSH iron sulfur domain2 (CISD2) is an evolutionarily conserved gene. It functions to control mammalian life span and regulate human breast cancer cells proliferation. However, the characteristics of CISD2 expression and its clinical/prognostic significance are unclear in human tumor. Our study aimed to investigate the expression pattern and clinicopathological significance of CISD2 in patients with early-stage cervical cancer. The mRNA and protein expression levels of CISD2 were analyzed in eight cervical cancer cell lines and eight paired cervical cancer tumors by real-time PCR and Western blotting, respectively. Immunohistochemistry was performed to examine CISD2 protein expression in paraffin-embedded tissues from 149 early-stage cervical cancer patients. Statistical analyses were used to evaluate the clinicopathological significance of CISD2 expression. CISD2 expression was significantly upregulated in cervical cancer cells at both the mRNA and protein levels. Statistical analysis showed a significant correlation of CISD2 expression with the squamous cell carcinoma antigen (P = 0.000), myometrium invasion (P = 0.003), recurrence (P = 0.012), lymphovascular space involvement (P = 0.019) and especially pelvic lymph node metastasis (PLNM; P = 0.000). Patients with higher CISD2 expression had shorter overall survival duration than patients with lower CISD2 expression. Multivariate analysis suggested that CISD2 expression might be an independent prognostic indicator for the survival of patients with early-stage cervical cancer. Our results for the first time suggested that high CISD2 expression was closely correlated with PLNM and poor prognosis in early-stage cervical cancer patients. CISD2 protein might be a novel biomarker for early-stage cervical cancer progression.