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

BUCCI MUÑOZ MARIA; GOLA ALDANA MAGALI; LIVORE, VERÓNICA INÉS; MOTTINO, ALDO DOMINGO

Mar del Plata

Congreso; SAIC, SAI, SAFIS; 2022

SAIC, SAI, SAFIS

IGF2BP1 is an RNA-binding protein and serves as a post-transcriptional fine-tuner regulating the expression of its mRNAs target. Its expression was found to promote hepatocarcinoma (HCC) cell proliferation, migration, invasion and correlates with poor survival and prognosis. Sfb is a first-line therapy used for HCC. Sfb resistance still remains one of the major causes of treatment failure and often involves ABC transporters upregulation, like ABCB1. We showed that IGF2BP1 constitutive levels are involved in regulation of ABCB1 expression, that Sfb induced IGF2BP1 and ABCB1 protein expression and that IGF2BP1 depletion prevented IGF2BP1 and ABCB1 induction by Sfb in HepG2 cells. We aim to elucidate the molecular mechanism of ABCB1 induction by Sfb and the role of IGF2BP1 in this event. HepG2 cells were incubated with Sfb 2µM or DMSO (control; C) for 24h, 48h and 72h. To evaluate IGF2BP1 participation in ABCB1 upregulation by Sfb, IGF2BP1 was transiently knocked down with a siRNA targeting human IGF2BP1 mRNA (IGF2BP1 siRNA) or scrambled (C siRNA) as control. Cells were treated, 24h after transfection, with Sfb 2µM for 48h. IGF2BP1 and ABCB1 mRNA levels were measured by Real Time PCR. Data was presented as mean±SEM, n=3-6, *p