Loss of BRMS2 induces cell growth inhibition and translation capacity reduction in colorectal cancer cells.

A variety of chemotherapeutic drugs targeting ribosome processing have been developed and applied to cancer treatment mainly based on the impaired ribosome biogenesis checkpoint (IRBC). The IMP U3 small nucleolar ribonucleoprotein 3 (IMP3, BRMS2) has been identified as a participant in pre-rRNA processing for nearly twenty years. However, the roles of BRMS2 in cancers still unknown. In this research, a tissue microarray (TMA) with 151 paired tissues showed the aberrant overexpression of BRMS2 in CRC tissues which was associated with the worse prognosis. To clarify the function of BRMS2 in CRC cells, an inducible knockdown system was introduced and and the cell growth was drastically suppressed. Mechanistically, we found depletion of BRMS2 markedly decreased the protein translation rates which can limit cell growth. Furthermore, to confirm whether the IRBC played a role, multiple approaches including detection of the p53 pathway, depletion of BRMS2 in p53-mutated SW620 cells, and co-depletion of RPL11 were taken. To our surprise, IRBC was not activated. That indicated BRMS2 may play a unique role in ribosome biosynthesis and IRBC. Taken together, our results demonstrated the oncogenic function of BRMS2 in CRC cells and supported its potential as a therapeutic target.