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Background: Oncocytic carcinoma of the breast is extremely rare, and its molecular profile is poorly understood. The distinctive feature of oncocytic carcinoma of the breast is that the granular eosinophilic cytoplasm contains numerous mitochondria. Recently, microRNA-146a-5p has been identified as a contributor to carcinogenesis and as a mitochondria-related microRNA, which regulates the mitochondrial function affecting Bcl-2. Bcl-2 plays a role in mitochondrial apoptosis.Case presentation: We report the clinical features, histopathological features, and immunohistochemical and molecular findings of oncocytic carcinoma of the breast in a 76-year-old woman. Immunohistochemistry studies revealed that the tumor cells were positive for antimitochondrial antibody but negative for gross cystic disease fluid protein 15, which confirmed the diagnosis. For molecular profiling, expression of microRNA-146a-5p and Bcl-2 messenger RNA (mRNA), which are mitochondria-related small molecules, were evaluated using real-time reverse transcription polymerase chain reaction. We found that the expression of microRNA-146a-5p was significantly lower (p < 0.01) and that of Bcl-2 mRNA was significantly higher (p < 0.01) compared to the control group (with no specific type of breast cancer). Conclusions: The significant changes in the expression of microRNA-146a-5p and Bcl-2 are specific to oncocytic carcinoma of the breast. Therefore, we suggest that the use of microRNA-146a-5p to target Bcl-2 has a potential therapeutic effect on oncocytic carcinoma of the breast.

The abnormal deposition of amyloids by amyloid-β protein (Aβ) is a pathological hallmark of Alzheimer's disease (AD). Aged rodents rarely develop the characteristic lesions of the disease, which is different from the case in humans. Rodent Aβ (rAβ) differs from human Aβ (hAβ) only in the three substitutions of Arg to Gly, Tyr to Phe, and His to Arg at positions 5, 10, and 13, respectively. Understanding the reason why rodent Aβ does not form amyloids is important to revealing factors that cause the abnormal aggregation of Aβ under pathologic conditions. We have proposed that the binding of Aβ to membranes with ganglioside clusters plays an important role in the abnormal aggregation of Aβ. In this study, we compared hAβ and rAβ in terms of aggregation on neuronal cells, on raftlike model membranes, and in buffer. We found that rAβ formed amyloid fibrils similar to those of hAβ in buffer solution. In contrast, on cell membranes and raftlike membranes, hAβ formed toxic, mature amyloid fibrils, whereas rAβ produced less toxic protofibrils that were not stained by the amyloid-specific dye Congo red. Thus, our ganglioside cluster-mediated amyloidogenesis hypothesis explains the immunity of rodents from cerebral Aβ amyloid deposition, strengthening the importance of ganglioside clusters as a platform of abnormal Aβ deposition in the pathology of AD.

The microRNA miR-22 targets CDK6, SIRT1, and Sp1—genes involved in regulation of the senescence program—to suppress cell growth and proliferation., Cellular senescence acts as a barrier to cancer progression, and microRNAs (miRNAs) are thought to be potential senescence regulators. However, whether senescence-associated miRNAs (SA-miRNAs) contribute to tumor suppression remains unknown. Here, we report that miR-22, a novel SA-miRNA, has an impact on tumorigenesis. miR-22 is up-regulated in human senescent fibroblasts and epithelial cells but down-regulated in various cancer cell lines. miR-22 overexpression induces growth suppression and acquisition of a senescent phenotype in human normal and cancer cells. miR-22 knockdown in presenescent fibroblasts decreased cell size, and cells became more compact. miR-22–induced senescence also decreases cell motility and inhibits cell invasion in vitro. Synthetic miR-22 delivery suppresses tumor growth and metastasis in vivo by inducing cellular senescence in a mouse model of breast carcinoma. We confirmed that CDK6, SIRT1, and Sp1, genes involved in the senescence program, are direct targets of miR-22. Our study provides the first evidence that miR-22 restores the cellular senescence program in cancer cells and acts as a tumor suppressor.