The Pseudogene DUXAP8 Promotes Colorectal Cancer Cell Proliferation, Invasion, and Migration by Inducing Epithelial-Mesenchymal Transition Through Interacting with EZH2 and H3K27me3.

Background: Colorectal cancer (CRC) is the third leading cause of cancer death worldwide. The long noncoding RNA (lncRNA) DUXAP8 has been reported to play an important role in CRC. This study investigated the mechanism by which this lncRNA regulates CRC progression.

Methods: The levels of lncRNA DUXAP8 in CRC tissues and cell lines were detected by qRT-PCR. We then knocked down or forced overexpression of DUXAP8, and the resultant effect on cell proliferation was determined by the Edu assay and a cell cycle analysis, and the effect on cell apoptosis was determined by flow cytometry. The cell invasion/migration ability and the epithelial-to-mesenchymal transition (EMT) markers were determined by Transwell/wound healing assays and Western blotting. CHIP and RNA pull-down assays were performed to determine the binding of Zeste gene enhancer 2 (EZH2) and trimethylated histone H3 to Lys27 (H3K27me3) in the E-cadherin promoter regions, or to DUXAP8.

Results: The levels of lncRNA DUXAP8 were significantly increased in CRC tissues and CRC cell lines. Knockdown of lncRNA DUXAP8 inhibited cell proliferation and the EMT process, and increased cell apoptosis, and overexpression of lncRNA DUXAP8 had an opposite effect. Both ChIP and RNA pull-down assays showed that the E-cadherin promoter region was bound by H3K27me3 and EZH2, which restrained E-cadherin expression. However, that binding was suppressed and E-cadherin expression was markedly induced by lncRNA DUXAP8 knockdown. Furthermore, lncRNA DUXAP8 could interact with EZH2 and H3K27me3.

Conclusion: Our data indicated that lncRNA DUXAP8 could induce the progression of CRC by negatively regulating E-cadherin via interaction with EZH2 and H3K27me3. These findings suggest lncRNA DUXAP8 as target for treating CRC.