Anti-tumour efficacy of mitofusin-2 in urinary bladder carcinoma

Abstract

Mitochondrial GTPase mitofusin-2 gene (Mfn2) is a novel gene characterised as a cell proliferation inhibitor. Mfn2 protein over-expression, mediated by an adenovirus, has a significant anti-tumour effect in A548 and HT-29 cells. However, there is no report on the effect of Mfn2 on urinary bladder carcinoma (UBCC). In this study, we sought to investigate the function of Mfn2 in UBCC. Mfn2 expression in 36 paired UBCC samples was investigated by reverse transcription-polymerase chain reaction and Western blot analyses. An adenovirus encoding the complete Mfn2 open reading frame (Ad-Mfn2) was used to infect UBCC cells, and an adenoviral vector encoding green fluorescent protein (Ad-GFP) was used as a control. The effects of Mfn2 on cell-cycle distribution and apoptosis were assessed by flow cytometry and Western blot analyses. The Mfn2 protein showed significantly lower expression in UBCC tissues than nearby non-tumourous tissues. Ad-Mfn2 exhibited a significant anti-tumour effect in T24 and 5,637 cells. Mfn2 overexpression in T24 cells significantly inhibited cell proliferation, by arresting the transition of the cell cycle from the G(1) to S phase, and induced apoptosis by upregulating active caspase-3 and cleaved PARP levels. Mfn2 also induced increased p21 and p27 expression levels, but down-regulated PCNA levels. These findings indicate that Mfn2 is a potential UBCC tumour suppressor gene, which showed significantly lower expression in tumour tissues than adjacent non-tumourous tissues and could promote apoptosis and inhibit the proliferation of UBCC cells. Mfn2 may become an important therapeutic target for treating UBCC.