TET-mediated sequestration of miR-26 drives EZH2 expression and gastric carcinogenesis

DNA demethylases of the TET family function as tumor suppressors in various human cancers but their pathogenic contributions and mechanisms of action in gastric carcinogenesis and progression remain unclear. Here we report that TET is transcriptionally upregulated in gastric cancer (GC) where it correlates with poor prognosis. Mechanistic investigations revealed that TET facilitated gastric carcinogenesis through a non-coding function of the 3'UTR which interacted with miR-26. This interaction resulted in sequestration of miR-26 from its target EZH2, which released the suppression on EZH2, and thereby leaded to EZH2 overexpression in gastric cancer. Our findings uncover a novel non-coding function for TET family proteins in facilitating gastric carcinogenesis.

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