Small non-coding RNA landscape is modified by GPAT2 silencing in MDA-MB-231 cells

LACUNZA, E.; MONTANARO, M.A.; SALVATI, A; MEMOLI, D.; RIZZO, F.; HENNING, M.F.; QUIROGA, I.Y.; GUILLOU, H.; ABBA, M.; GONZALEZ BARO, M.R.; WEISZ, A.; PELLON-MAISON, M.

Oncotarget

Impact Journals, LLC

Año: 2018 vol. 9 p. 28141 - 28145

Glycerol-3-phosphate acyltransferase-2 is a member of ?cancer-testis gene?family. Initially linked to lipid metabolism, this gene has been recently found involvedalso in PIWI-interacting RNAs biogenesis in germline stem cells. To investigate itsrole in piRNA metabolism in cancer, the gene was silenced in MDA-MB-231 breastcancer cells and small RNA sequencing was applied. PIWI-interacting RNAs andtRNA-derived fragments expression profiles showed changes following GPAT2silencing. Interestingly, a marked shift in length distribution for both small RNAswas detected in GPAT2-silenced cells. Most downregulated PIWI-interacting RNAsare single copy in the genome, intragenic, hosted in snoRNAs and previously found tobe upregulated in cancer cells. Putative targets of these PIWI-interacting RNAs arelinked to lipid metabolism. Downregulated tRNA derived fragments derived from, socalled?differentiation tRNAs?, whereas upregulated ones derived from proliferationlinkedtRNAs. miRNA amounts decrease after Glycerol-3-phosphate acyltransferase-2silencing and functional enrichment analysis of deregulated miRNA putative targetspoint to mitochondrial biogenesis, IGF1R signaling and oxidative metabolism of lipidsand lipoproteins. In addition, miRNAs known to be overexpressed in breast cancertumors with poor prognosis where found downregulated in GPAT2-silenced cells. Inconclusion, GPAT2 silencing quantitatively and qualitatively affects the population ofPIWI-interacting RNAs, tRNA derived fragments and miRNAs which, in combination,result in a more differentiated cancer cell phenotype.