MOLECULAR BASIS OF ABCB1 INDUCTION BY SORAFENIB (SFB) IN HEPG2 CELLS. ROLE OF INSULIN- LIKE GROWTH FACTOR 2 MRNA-BINDING PROTEIN 1 (IGF2BP1)

BUCCI-MUÑOZ, MARÍA; GOLA, ALDANA MAGALÍ; LIVORE V; MOTTINO, ALDO DOMINGO; CEBALLOS MARÍA PAULA; RUIZ MARÍA LAURA

Mar del Plata

Congreso; Reunion anual de Biociencias; 2022

IGF2BP1 is an RNA-binding protein and serves as a post-transcriptionalfine-tuner regulating the expression of its mRNAs target. Itsexpression was found to promote hepatocarcinoma (HCC) cell proliferation,migration, invasion and correlates with poor survival andprognosis. Sfb is a first-line therapy used for HCC. Sfb resistancestill remains one of the major causes of treatment failure and ofteninvolves ABC transporters upregulation, like ABCB1. We showedthat IGF2BP1 constitutive levels are involved in regulation of ABCB1expression, that Sfb induced IGF2BP1 and ABCB1 protein expressionand that IGF2BP1 depletion prevented IGF2BP1 and ABCB1induction by Sfb in HepG2 cells. We aim to elucidate the molecularmechanism of ABCB1 induction by Sfb and the role of IGF2BP1in this event. HepG2 cells were incubated with Sfb 2μM or DMSO(control; C) for 24h, 48h and 72h. To evaluate IGF2BP1 participationin ABCB1 upregulation by Sfb, IGF2BP1 was transiently knockeddown with a siRNA targeting human IGF2BP1 mRNA (IGF2BP1 siRNA)or scrambled (C siRNA) as control. Cells were treated, 24h aftertransfection, with Sfb 2μM for 48h. IGF2BP1 and ABCB1 mRNAlevels were measured by Real Time PCR. Data was presented asmean±SEM, n=3-6, *p