Anti-tumour Efficacy Of Mitofusin-2 In Urinary Baldder Carcinoma

Objectives:Mitofusion 2 (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). Here, we sought to investigate the function of Mfn2 in UBCC.Materials and methods: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. Results: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 5637 cells. Mfn2 overexpression in T24 cells significantly inhibited cell proliferation, by arresting the transition of the cell cycle from the G1 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.Conclusions: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.