U2 small nuclear RNA auxiliary factor 2, transcriptionally activated by the transcription factor Dp-1/E2F transcription factor 1 complex, enhances the growth and aerobic glycolysis of leiomyosarcoma cells

The dysregulation of U2 Small Nuclear RNA Auxiliary Factor 2 (U2AF2) is associated with malignant behaviors of multiple types of tumors. In this study, we explored the association between <i>U2AF2</i> dysregulation and the survival of patients with primary leiomyosarcoma, the regulatory effect of U2AF2 on cell growth/aerobic glycolysis, and the mechanisms of <i>U2AF2</i> dysregulation at the transcriptional level. Gene expression and survival time of patients with primary leiomyosarcoma were extracted from TCGA-Sarcoma (SARC). Leiomyosarcoma cell lines SK-LMS-1 and SK-UT-1 were utilized to construct <i>in vitro</i> and <i>in vivo</i> models. Results showed that the higher <i>U2AF2</i> expression group had significantly shorter progression-free survival (HR: 2.049, 95%CI: 1.136–3.697, <i>p</i> = 0.011) and disease-specific survival (4.656, 95%CI: 2.141–10.13, <i>p</i> &lt; 0.001) compared to the lower <i>U2AF2</i> expression group. <i>U2AF2</i> knockdown suppressed leiomyosarcoma cell growth and aerobic glycolysis (decreased glucose uptake, lactate production, and extracellular acidification rate) <i>in vitro</i>. Tumors derived from SK-LMS-1 cells with <i>U2AF2</i> knockdown grew significantly slower, with lower GLUT1, PGK1, and PGAM1 protein expression than the control groups. TFDP1 and E2F1 could interact with each other in leiomyosarcoma cells. Both TFDP1 and E2F1 could bind to the promoter of <i>U2AF2</i> and exert a synergistic activating effect on <i>U2AF2</i> transcription. In conclusion, this study revealed that <i>U2AF2</i> upregulation is associated with poor survival of leiomyosarcoma. Its upregulation enhances proliferation and aerobic glycolysis of leiomyosarcoma cells <i>in vitro</i> and <i>in vivo</i>. TFDP1 and E2F1 can form a complex, which binds to the <i>U2AF2</i> gene promoter and synergistically activates its transcription.