Identification of three 11p11.2 candidate liver tumor suppressors through analysis of known human genes

Abstract

We have previously mapped a liver tumor suppressor locus to human chromosome 11p11.2-p12 using a functional model of tumor suppression. Using this model system, we have employed a candidate gene approach to identify potential liver tumor suppressor genes. Thirty-eight known genes have been positioned in human 11p11.2-p12 by the Human Genome Project. Here we show that four of these genes (guanine nucleotide binding protein gamma 3; mitochondrial carrier homolog 2; p53-induced protein (PIG11), and pRDI-BF1-rIZ1 domain containing 11) localized to the minimal liver tumor suppressor region within 11p11.2-p12. In fact, all of these genes mapped to human 11p11.2, allowing refinement of the liver tumor suppressor region to this cytogenetic band. Three of the four genes (mitochondrial carrier homolog 2, PIG11, and pRDI-BF1-rIZ1 domain containing 11) were uniformly expressed by an index panel of suppressed microcell hybrid cell lines, identifying them as candidate liver tumor suppressor genes. In a preliminary analysis of four human hepatocellular carcinoma cell lines (HepG2, Hep3B, SNU398, and SNU449), the transcript for PIG11 was lost or significantly decreased in two of these cell lines (HepG2 and Hep3B), suggesting the potential involvement of PIG11 in some human hepatocellular carcinomas. The results of this study extended our previous knowledge of genes located in the minimal liver tumor suppressor region of human 11p11.2 and identified several candidate liver tumor suppressor genes from this region. Further characterization of these candidates will provide new insight into the role of human 11p11.2 in the molecular pathogenesis of human liver cancer.

Loss of PRDM11 promotes MYC-driven lymphomagenesis

“…by guest www.bloodjournal.org From molecular etiology behind many cancers. Interestingly, the chromosomal region of PRDM11 has previously been associated with tumor suppression, 38,39 and we demonstrate here, for the first time, a tumor suppressor role for Prdm11 in vivo.…”

Silencing SMYD3 in hepatoma demethylates RIZI promoter induces apoptosis and inhibits cell proliferation and migration

“…In addition, different SMYD3 expression levels in hepatoma cells was also consistent with RIZ1 promoter methylation and mRNA expression in hepatoma cells in our results (data not shown) and in other results. HepG2 cells have been shown to lack RIZ1 expression due to promoter hypermethylation; in contrast, Hep3B cells do not show RIZ1 promoter hypermethylation and express RIZ1 mRNA [26,27] . These results strongly suggest that SMYD3 plays a role in HCC development and progression, partly through RIZ1 promoter hypermethylation and RIZ1 inactivation.…”

Re-expression of tumorigenicity after attenuation of human synaptotagmin 13 in a suppressed microcell hybrid cell line

“…The human chromosome 11 liver tumor suppressor locus was identified through deletion mapping of microcell hybrid cell lines derived from GN6TF rat liver tumor cells (9). The minimal liver tumor suppressor region of human 11p11.2 contains a number of potential candidate tumor suppressor genes (10)(11)(12). However, transcription mapping of suppressed and non-suppressed microcell hybrid cell lines reduced the number of viable candidate genes and produced evidence suggesting that SYT13 is the best candidate for the human 11p11.2 liver tumor suppressor (11).…”

“…Genomic mapping localized the liver tumor suppressor locus to a small (<1 Mbp) region of human chromosome 11p11.2 containing a number of candidate genes (9,10). Subsequently, transcription mapping identified several candidate 11p11.2 tumor suppressor genes (including TP53I11, PRDM11, LOC219638 and SYT13) that were expressed in a panel of suppressed microcell hybrid cell lines (11,12). SYT13 mRNA was detected in 100% of suppressed microcell hybrid cell lines and was absent in all non-suppressed clones, including a non-suppressed microcell hybrid cell line that contains chromosome 11 with an …”