Identification of NOL8, a nucleolar protein containing an RNA recognition motif (RRM), which was overexpressed in diffuse-type gastric cancer.

In an attempt to identify novel therapeutic targets for diffuse-type gastric cancer, we had previously compared expression profiles of 20 diffuse-type gastric-cancer tissues with corresponding non-cancerous mucosae by means of a cDNA microarray consisting of 23,040 genes. Among 153 genes whose expression levels were elevated in cancers compared to non-cancerous mucosae, we focused on a gene termed NOL8 that encodes a putative 150-kDa protein with an RNA-recognition motif (RRM) domain in its amino-acid terminal region. Comparison of expression profiles between diffuse-type and intestinal-type gastric cancers showed that NOL8 was specifically up-regulated in diffuse-type cancers. Northern blot analysis revealed that NOL8 was expressed in skeletal muscle, but not expressed or hardly detectable in 22 other tissues examined. Immunocytochemical staining of NOL8 showed specific localization in the nucleolus. Subsequent protein phosphatase analysis coupled with western analysis revealed the presence of the phosphorylated form. Furthermore, transfection of short-interfering RNA (siRNA) specific to NOL8 into three diffuse-type gastric cancer cells, St-4, MKN45 and TMK-1, effectively reduced expression of this gene and induced apoptosis in these cells. These findings provide a new insight into diffuse-type gastric carcinogenesis and may contribute to the development of new therapeutic strategies for diffuse-type gastric cancer.