@entity1 @entity19683 pyrophosphatase 1 promotes @entity0 cell growth and XXXX through the modulation on @entity73070 metabolism and global hypomethylation.

@entity1 @entity10021 @entity3308 @entity0 @entity19683 @entity5 @entity15652 @entity9953 @entity73070
UNASSIGNED: @entity1 @entity15652 ( @entity19683 pyrophosphatase 1), also known as @entity15652 , belongs to MazG-like @entity9953 pyrophosphatase (NTP-PPase) superfamily. Being a newly identified pyrophosphatase, its relevance to tumorigenesis and the mechanisms are not well investigated. In the present study, we have confirmed our previous study that @entity15652 was significantly hyperexpressed in @entity0 and further demonstrated its strong association with @entity5 progression and poor prognosis in @entity0 . Knockdown of @entity15652 in @entity0 cell line MCF-7 cells remarkably retarded proliferation and colony formation in vitro. The capacity of mammosphere formation of MCF-7 was suppressed with the silence of @entity15652 , which was consistent with the enhanced mammosphere-forming ability in @entity15652 -overexpressed MDA-MB-231 cells. To further dissect the mechanisms of @entity15652 in promoting @entity5 cell growth and @entity3308 maintenance, its biochemical properties and biological functions were investigated. @entity15652 displayed bioactive form with tetrameric structure similar to other MazG domain-containing pyrophosphatases based on structure simulation. A substrate preference for @entity19683 and its methylated or @entity10021 -modified derivatives over the other canonical (deoxy-) NTPs was demonstrated from enzymatic assay. This substrate preference was also proved in @entity0 cells that the intracellular @entity73070 level increased in @entity15652 -deficient MCF-7 cells but decreased in @entity15652 -overexpressed MDA-MB-231 cells. Moreover, global methylation level was elevated in @entity15652 -knockdown MCF-7 cells or mammosphere-forming MCF-7 cells but decreased significantly in @entity15652 -overexpressed MDA-MB-231 cells and its mammospheres. Our results thus indicated that @entity1 @entity15652 was capable of modulating the concentration of intracellular @entity73070 . This in turn affected global methylation, contributing to a known phenomenon of hypomethylation related to the @entity5 cell growth and @entity3308 maintenance. Our current investigations point to the pathological functions of @entity15652 overexpression in @entity0 cells with aberrant @entity19683 metabolism and epigenetic modification.
