UBE2S targets RPL26 for ubiquitination and degradation to promote non-small cell lung cancer progression via regulating c-Myc.

ABSTRACT

Multiple studies have shown that E2 conjugating enzyme family are dysregulated in various cancers and associated with tumor progression and poor prognosis. In present study, we screened and confirmed that UBE2S is one of the E2 conjugating enzymes highly expressed in non-small cell lung cancer (NSCLC), and it plays an oncogenic role by enhancing cell proliferation, migration and stemness in vitro. Using immunoprecipitation technology combined with mass spectrometry assay, we identified ribosomal protein RPL26 as the substrate protein of UBE2S in NSCLC. At the molecular level, overexpression of UBE2S accelerated the ubiquitination and degradation of RPL26, thus upregulating c-Myc to enhance the progression of NSCLC. In addition, the results of a xenograft experiment showed that inhibiting UBE2S could suppress RPL26-c-Myc mediated NSCLC tumor growth in vivo. Our data provided mechanistic evidence supporting the existence of a novel UBE2S-RPL26-c-Myc axis and its critical contribution to progression of NSCLC.