Homo sapiens longevity assurance homologue 2 of yeast LAG1 (LASS2), also known as
tumor metastasis suppressor gene 1 (TMSG1), is a newly found
tumor metastasis suppressor gene in 1999. Preliminary studies showed that it not only suppressed
tumor growth but also closely related to
tumor metastasis, however, its molecular mechanisms is still unclear. There have been reported that
protein encoded by LASS2/TMSG-1 could directly interact with the C subunit of
Vacuolar ATPase (V-
ATPase), which suggested that LASS2/TMSG1 might inhibit the invasion and
metastasis through regulating the function of V-
ATPase. Thus, in this study, we explored the effect of small interference RNA (
siRNA) targeting LASS2/TMSG1 on the invasion of human prostate
carcinoma cell line PC-3M-2B4 and its molecular mechanisms associated with the V-
ATPase. Real-time fluorogentic quantitative PCR (RFQ-PCR) and Western blot revealed dramatic reduction of 84.5% and 60% in the levels of LASS2/TMSG1
mRNA and
protein after transfection of
siRNA in PC-3M-2B4 cells. The V-
ATPase activity and extracellular hydrogen ion concentration were significantly increased in 2B4 cells transfected with the LASS2/TMSG1-
siRNA compared with the controls. The activity of secreted MMP-2 was up-regulated in LASS2/TMSG1-
siRNA treated cells compared with the controls; and the capacity for migration and invasion in LASS2/TMSG1-
siRNA treated cells was significantly higher than the controls. Thus, we concluded that silencing of LASS2/TMSG1 may promote invasion of
prostate cancer cell in vitro through increase of V-
ATPase activity and extracellular hydrogen ion concentration and in turn the activation of secreted MMP-2.