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The present study aimed to investigate the biological role of the mitochondrial GTPase mitofusin-2 (MFN2) in bladder cancer. MFN2 mRNA expression in tumor and paired adjacent non-tumor tissues from 8 patients was investigated using reverse transcription-quantitative polymerase chain reaction analysis. Immunohistochemistry was used to investigate MFN2 expression in 117 bladder cancer specimens. The associations of MFN2 expression with clinicopathological parameters were evaluated statistically. In addition, the biological role of MFN2 in the proliferation, migration and invasion of bladder cancer cells was examined. It was identified that MFN2 expression was significantly downregulated in bladder cancer tissues compared with normal tissues. MFN2 expression was associated with tumor stage, tumor grade and lymph node status. Furthermore, patients with low MFN2 expression demonstrated a shorter overall survival time (P=0.025). MFN2 knockdown by small interfering RNA promoted cancer cell proliferation, migration and invasion in vitro, and enhanced tumor progression in vivo. Mechanistically, MFN2 was revealed to be involved in Wnt/β-catenin signaling. In conclusion, MFN2 may serve as a potential therapeutic target in the treatment of bladder cancer, and the progress of bladder cancer may be delayed by regulating MFN2 expression. [ABSTRACT FROM AUTHOR]

Mitofusin 2 (Mfn2) is expressed in numerous human tissues and serves a pivotal role in cell proliferation. However, Mfn2 is considered as an anti-tumor gene, and is silenced in human malignant tumors, including those of breast cancer. However, the mechanisms contributing to Mfn2 silencing and the mechanism of its anti-tumor function in breast cancer remain unclear. In the present study, hypoexpression of Mfn2, and hypermethylation of its promoter, was confirmed in human breast cancer cells and in breast cancer tissues by reverse transcription-quantitative polymerase chain reaction (PCR) and methylation specific PCR, respectively. Chemical demethylation treatment with 5-aza-2'-deoxycytidine upregulated the mRNA expression level of Mfn2 in MCF-7 cells in a dose-dependent manner. In addition, overexpression of Mfn2 repressed the proliferation, migration and invasion of MCF-7 cells, mediated by inhibition of the Ras-extracellular signal-regulated kinase (ERK)1/2 signaling pathway. However, overexpression of Mfn2 with deletion of the p21Ras motif (Mfn2ΔRas) and protein kinase A (PKA) phosphorylation site (Mfn2ΔPKA) partially reduced the anti-tumor function of Mfn2, and inhibited the Ras-ERK1/2 signaling pathway. Taken together, the present study confirmed the anti-tumor effects of Mfn2 in human breast cancer and clarified that the mechanism of its anti-tumor functions includes promoter DNA methylation, the P21Ras binding site and PKA phosphorylation. [ABSTRACT FROM AUTHOR]

Cancer cachexia remains a leading cause of morbidity and mortality worldwide, despite extensive research and clinical trials. The prominent clinical feature of cancer cachexia is the continuous loss of skeletal muscle that cannot be fully reversed by conventional nutritional support, and that leads to progressive functional impairment. The mechanism underlying muscle loss in patients with cachexia is poorly understood. The present study analyzed 21 cancer patients with or without cachexia, and demonstrated that mitofusin-2 (Mfn2) was downregulated in the rectus abdominis of patients with cachexia, which was associated with body weight loss. In vitro cell experiments indicated that loss of Mfn2 was associated with atrophy of the C2C12 mouse myoblast cell line. Furthermore, in vivo animal experiments demonstrated that cachexia decreased gastrocnemius muscle mass and Mfn2 expression, and overexpression of Mfn2 in gastrocnemius muscle was able to partially attenuate cachexia-induced gastrocnemius muscle loss. The results of the present study suggested that Mfn2 is involved in cachexia-induced muscle loss and may serve as a potential target for therapy of cachexia. [ABSTRACT FROM AUTHOR]

The mitochondrial GTPase mitofusin-2 (Mfn2) gene is a novel gene characterized as a cell proliferation inhibitor. Mfn2 has previously been reported to play a role in regulating cell proliferation, apoptosis and differentiation in a number of cell types. However, there are no studies on the effect of Mfn2 in breast cancer. In this study, we aimed to elucidate the function and mechanism of Mfn2 in breast cancer. A plasmid encoding the complete Mfn2 open reading frame (pEGFP-Mfn2) was used to infect breast cancer cells. The effect of Mfn2 on proliferation was assessed by methyl thiazolyl tetrazolium and bromodeoxyuridine incorporation analyses. Flow cytometry, immunofluorescence and western blot analyses were used to test the effects of Mfn2 on cell cycle distribution and apoptosis. Additionally, the PI3K/Akt signaling pathway was analyzed after pEGFP-Mfn2 was transfected into MCF-7 cells. The results revealed that Mfn2 suppressed the proliferation of MCF-7 cells by regulating more cells at the G0/G1 phase and decreasing proliferating cell nuclear antigen and cyclin A expression. The results also demonstrated that the PI3K/Akt signaling pathway is involved in Mfn2-regulated proliferation and apoptosis. Taken together, this indicates that Mfn2 mediates MCF-7 cell proliferation and apoptosis via the PI3K/Akt signaling pathway. Mfn2 may thus be a significant therapeutic target in the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Mitofusin 2 ( Mfn2 ) is expressed in numerous human tissues and serves a pivotal role in cell proliferation. However, Mfn2 is considered as an anti-tumor gene, and is silenced in human malignant tumors, including those of breast cancer. However, the mechanisms contributing to Mfn2 silencing and the mechanism of its anti-tumor function in breast cancer remain unclear. In the present study, hypoexpression of Mfn2 , and hypermethylation of its promoter, was confirmed in human breast cancer cells and in breast cancer tissues by reverse transcription-quantitative polymerase chain reaction (PCR) and methylation specific PCR, respectively. Chemical demethylation treatment with 5-aza-2'-deoxycytidine upregulated the mRNA expression level of Mfn2 in MCF-7 cells in a dose-dependent manner. In addition, overexpression of Mfn2 repressed the proliferation, migration and invasion of MCF-7 cells, mediated by inhibition of the Ras-extracellular signal-regulated kinase (ERK)1/2 signaling pathway. However, overexpression of Mfn2 with deletion of the p21 Ras motif ( Mfn2 ΔRas ) and protein kinase A (PKA) phosphorylation site ( Mfn2 ΔPKA ) partially reduced the anti-tumor function of Mfn2, and inhibited the Ras-ERK1/2 signaling pathway. Taken together, the present study confirmed the anti-tumor effects of Mfn2 in human breast cancer and clarified that the mechanism of its anti-tumor functions includes promoter DNA methylation, the P21 Ras binding site and PKA phosphorylation.