The Reprimo Gene Family: A Novel Gene Lineage in Gastric Cancer with Tumor Suppressive Properties

Abstract

The reprimo (RPRM) gene family is a group of single exon genes present exclusively within the vertebrate lineage. Two out of three members of this family are present in humans: RPRM and RPRM-Like (RPRML). RPRM induces cell cycle arrest at G2/M in response to p53 expression. Loss-of-expression of RPRM is related to increased cell proliferation and growth in gastric cancer. This evidence suggests that RPRM has tumor suppressive properties. However, the molecular mechanisms and signaling partners by which RPRM exerts its functions remain unknown. Moreover, scarce studies have attempted to characterize RPRML, and its functionality is unclear. Herein, we highlight the role of the RPRM gene family in gastric carcinogenesis, as well as its potential applications in clinical settings. In addition, we summarize the current knowledge on the phylogeny and expression patterns of this family of genes in embryonic zebrafish and adult humans. Strikingly, in both species, RPRM is expressed primarily in the digestive tract, blood vessels and central nervous system, supporting the use of zebrafish for further functional characterization of RPRM. Finally, drawing on embryonic and adult expression patterns, we address the potential relevance of RPRM and RPRML in cancer. Active investigation or analytical research in the coming years should contribute to novel translational applications of this poorly understood gene family as potential biomarkers and development of novel cancer therapies.

The Reprimo gene family member, reprimo-like (rprml), is required for blood development in embryonic zebrafish

“…The Reprimo ( RPRM ) gene family is a group of single-exon genes exclusive to the vertebrate group, that diversified as a product of two rounds of whole genome duplications occurred in the last common ancestor of vertebrates between 676 and 615 million years ago 10–12 . The repertoire of Reprimo genes includes Reprimo ( RPRM ), Reprimo-like ( RPRML ) and Reprimo 3 ( RPRM3 ).…”

“…The repertoire of Reprimo genes includes Reprimo ( RPRM ), Reprimo-like ( RPRML ) and Reprimo 3 ( RPRM3 ). To date, only the human RPRM gene has been studied 10,12 , with no literature describing the role of RPRML or RPRM3 in either physiology or pathophysiology. In humans, RPRM is a highly glycosylated cytoplasmic protein, which has been characterized as a potential tumor-suppressor gene involved in the regulation of the p53 -mediated cell cycle arrest at G2 through the regulation of the Cdc2-cyclin B1 complex activity by a yet undiscovered mechanism 13 .…”

Identification of key genes and associated pathways in neuroendocrine tumors through bioinformatics analysis and predictions of small drug molecules

“…TTR (transthyretin) was responsible for progression of NET [63]. Methylation inactivation of tumor suppressor genes such as OGDHL (oxoglutarate dehydrogenase like) [64], CAMK2B [65] and RPRML (reprimo like) [66] were associated with progression of various cancer types, but loss of these genes might be liable for development of NET. Loss of tumor suppressor SRCIN1 was diagnosed with growth of gastric cancer [67], but loss of this gene might be linked with development of NET.…”

The Reprimo-Like Gene Is an Epigenetic-Mediated Tumor Suppressor and a Candidate Biomarker for the Non-Invasive Detection of Gastric Cancer

“…The second member of this gene family, RPRML , is also an intronless gene expressed at very low levels in most tissues according to the Genotype-Tissue Expression (GTEx) database ( ). Despite their low level of expression, these genes encode proteins with important biological functions [ 20 ]. In the present study, we evaluated the functional properties, clinical significance, and potential translational applications of RPRML , a hitherto uncharacterized member of the RPRM gene family in GC.…”