RBMY, a male germ cell-specific RNA-binding protein, activated in human liver cancers and transforms rodent fibroblasts

Abstract

The RNA-binding motif (RRM) gene on Y chromosome (RBMY), encoding a male germ cell-specific RNAbinding protein associated with spermatogenesis, was found inserted by hepatitis B virus (HBV) DNA in one childhood hepatocellular carcinoma (HCC). This study is aimed to explore the oncogenic potential of the RBMY protein. The RBMY transcripts, expressed exclusively in the testis of normal people, were detected by reverse transcription-polymerase chain reaction in 36% of HCCs from 90 males and in 67% of hepatoblastoma from six boys. The nontumor liver counter parts, cirrhotic liver tissues from children with biliary atresia, and other types of cancers, such as bile duct, colon, stomach, lung, prostate, and kidney, were all negative for RBMY expression. One to four types of RBMY transcripts, including wild type and variants with N-terminal RRM deletion, C-terminal SRGY (serine-arginine-glycine-tyrosine) boxes deletion, or deletion of both domains, were found in the testis and liver cancer tissues. The wild-type RBMY protein was expressed in the nucleus and demonstrated its tumorigenicity by transformation of mouse fibroblast NIH3T3 cells and in vivo tumor formation. The RBMY variant protein with deletion of C-terminal exons 9-12 was trapped in the cytoplasm and showed decreased tumorigenicity. Our results suggest that RBMY is a new candidate oncogene specific for male liver cancer.

Natural history of hepatitis B virus infection: pediatric perspective

“…Other mechanisms may be involved in the oncogenesis of pediatric HCC. The RBMY gene, which is a male germ cell-specific RNA-binding protein, is activated in about one-third of male HCC cases [64]. This may help to explain why gender is still important in pediatric HCC when the sex hormone may not be able to exert any influence.…”

Detection of Recurrent Copy Number Loss at Yp11.2 Involving TSPY Gene Cluster in Prostate Cancer Using Array-Based Comparative Genomic Hybridization

“…10, 26-28). It is not known, however, at which stage during prostate tumorigenesis the loss of Y chromosome occurs and how the genes on the Y chromosome contribute to tumorigenesis (29).…”

Sexual dimorphism in cancer

“…RBMY is aberrantly activated in male HCC 157 , where, like TSPY, it can enhance AR expression and activity as well as cancer development 158 (Fig. 3).…”