REGULATORY ROLE OF FABP5 IN LUNG ADENOCARCINOMA GENE EXPRESSION. A TRANSCRIPTOMIC APPROACH

COSTA, ML; GARCIA KA; ZADRA G; MINSKY D; CRESPO R; CORSICO B; SCAGLIA N

Congreso; LVI SAIB Meeting ?XV SAMIGE Meeting 2020; 2020

Cancer cells show a metabolic reprograming towards anabolism, required for cellular growth. Different pathways related tofatty acid (FA) metabolism are stimulated in cancer cells. Fatty acid-binding proteins (FABPs) are intracellular proteins thatbind FA and other hydrophobic ligands with high affinity. FABP5 overexpression has been associated to cancer onset andprogression, especially in breast and prostate, mainly by regulating peroxisome proliferator activated receptors (PPARs). Itsfunctions in lipid metabolism, however, are not fully understood. Recent studies from our laboratory, using chemical inhibitionand genetically modified cells, showed that FABP5 regulates lung adenocarcinoma (LUAD) lipid metabolism, cellproliferation and tumor growth in vivo. Thus, we studied the molecular mechanisms underlying the oncogenic effects ofFABP5, in particular, whether FABP5 regulates gene expression in LUAD. We found that FABP5 regulates the level ofproteins involved in FA metabolism (including fatty acid synthase and stearoyl-CoA desaturase 1) and cell cycle (cyclins B1and D1). Unexpectedly, reporter assays suggested that FABP5 regulates gene expression in a PPAR-independent manner. Togain further insights into the expression changes associated with FABP5, we analyzed the transcriptome of A549 LUAD cellstreated with the pan-FABP inhibitor HTS01037, compared to vehicle-treated controls, by RNA-Seq. FABP5 is the onlyisoform detected in this cell line, hence, HTS01037 can be regarded as a specific inhibitor in our model. Interestingly, wefound that FABP5 inhibition triggers profound changes in A549 cells transcriptome not previously associated with this protein.Although preliminary, our results suggest that FABP5 is an important transcriptional regulator in LUAD cells.