ROLE OF GPAT2 IN THE LANDSCAPE OF SMALL NON-CODING RNAs IN BREAST CANCER CELLS

SALVATI A; ABBA MC; PELLON MAISON M; MONTANARO MA; RIZZO F; WEISZ A; LACUNZA E; MEMOLI D; GONZALES BARO MR

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

GPAT2is expressed in the testis and ectopically overexpressed in cancer cells, whereit contributes to tumoral phenotype. Although GPAT2 was initially linked tolipid metabolism, it was demonstrated that it is essential for primary piRNAbiogenesis. In this work, we analyzed the impact of GPAT2 silencing in thelandscape of small noncoding RNAs of MDAMB231 cells. From the differentially expressed(DE) piRNAs, we found that most downregulated (down) piRNAs (32/39, 82%) aresingle copy in the genome being mainly intragenic (27/32, 84%), whereasupregulated (up) piRNAs are single (18/38, 47%) and multiple (20/38, 52%) copiesin a similar way. Interestingly, snoRNAs constituted the host gene of 81% ofthe intragenic single copy down piRNAs, which means 56% of total down piRNAs.Furthermore, many of down piRNAs were previously found upregulated in breastcancer growing cells. From the DE tRFs we identified 147 down and 128 up. DowntRFs would be derived from ?differentiation tRNAs? whereas up tRFs would befrom ?proliferation tRNAs?. Moreover, we obtained a protein profile from theamino acids carrying by DE tRFs and identified proteins associated tophosphatidic acid biosynthesis, phospholipid acyl chain remodeling andregulation of cell death. We also found a significant difference (p<0.05) inlength distribution of piRNAs and tRNAs reads among DE members. From DEexpressed miRNA, we identified 109 up and 104 down. Functional enrichment ofputative targets revealed specific terms associated to mitochondrialbiogenesis, IGF1R signaling, and oxidative metabolism of lipids andlipoproteins. GPAT2 silencing affect the length distribution of piRNAs and tRFs,and their specific abundance and features would define a less tumorigenicphenotype, as was previously observed in the silenced cells.  This finding could be indicative of a role ofGPAT2 in sncRNA processing, supported by the fact that other mitochondrialproteins have also been involved in at least piRNAs processing.