Discovery of a new gene affecting expression of cancer suppressor genes

September 17, 2021

The results are expected to contribute to cancer research and biomarkers to investigate the properties of cancer

RIKEN CSRS has discovered a new gene affecting the expression of a cancer suppressor gene in humans.

Conventional gene hunting has been done by excluding almost all genes possibly encoding short proteins and peptides consisting of fewer than 150 amino acids.

In this study, the group conducted proteogenomics analysis using transcriptomic and proteomic data of human cancer cell lines that can be obtained from public data repositories, and discovered a new gene encoding a short protein consisting of 120 amino acids. The gene was named "oSCRIB" as it overlapped partly with SCRIB gene, a tumor suppressor gene, on the human genome.

A recent study has shown that SCRIB gene also functions as a proto-oncogene, and it is considered important to maintain an appropriate level of its expression by avoiding both hyperexpression and underexpression for normal functioning of human cells. Therefore, the group employed biochemical methods and showed that oSCRIB gene suppresses the expression of SCRIB gene. This means that oSCRIB gene functions as a safeguard to suppress SCRIB overexpression in normal cells. In addition, reanalysis of human clinical proteomic data showed that the effect of oSCRIB gene as the safeguard for cells is weakened in cancer cells while SCRIB gene is highly expressed.

In addition to future cancer research, the results of this research are expected to be useful for the development of biomarkers to evaluate the properties of cancers and therapeutic effects of cancer treatment.

Original article
Communications Biology doi:10.1038/s42003-021-02619-8
Y. Nomura and N, Dohmae,
"Discovery of a small protein-encoding cis-regulatory overlapping gene of the tumor suppressor gene Scribble in humans".
Yuta Nomura; Postdoctoral Researcher
Naoshi Dohmae; Unit Leader
Biomolecular Characterization Unit