DNA hypermethylation of SHISA3 as a mechanism of gene inactivation and as a novel prognostic biomarker in colorectal cancer.

e14532 Background: Shisa3, a newly identified tumor suppressor, inhibits tumorigenesis and metastasis via counter-regulation of β-catenin in non-small cell lung cancer. However, its tumor suppressor role in other human cancers and the mechanism of gene inactivation still remain unknown. Methods: We validated the expression of SHISA3 gene by qRT-PCR. Then, we treated CRC cell lines with 5-aza-2’-deoxycytidine (5-Aza-CdR) and carried out bisulfate sequencing PCR and pyrosequencing in paired colorectal tumor and normal mucosa tissues to assess the DNA methylation status of SHISA3 gene. Results: We found that SHISA3 expression was significantly down-regulated in 34 (65.4%) of 52 colorectal carcinomas compared with corresponding normal mucosae by qRT-PCR. To explore the epigenetic silencing of SHISA3 gene, CRC cells were treated with DNA methylation inhibitor 5-Aza-CdR, and SHISA3 expression was obviously induced in four (66.7%) of six cell lines. CpG islands spanning SHISA3 gene were predicted via MethPrimer ...