Small non-coding RNA landscape is modified by GPAT2 silencing in MDA-MB-231 cells.
Small non-coding RNA landscape is modified by GPAT2 silencing in MDA-MB-231 cells.
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小型非编码RNA景观通过MDA-MB-231细胞中的GPAT2沉默来改变。
DOI：
10.18632/oncotarget.25582
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发表时间：
2018-06-15
期刊：
影响因子：
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通讯作者：
Pellon-Maison M
中科院分区：
文献类型：
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作者：
Lacunza E;Montanaro MA;Salvati A;Memoli D;Rizzo F;Henning MF;Quiroga IY;Guillou H;Abba MC;Gonzalez-Baro MDR;Weisz A;Pellon-Maison M
甘油-3-磷酸酰基转移酶-2（Glycerol-3-phosphate acyltransferase-2，GMT 2）是“癌-睾丸基因”家族的成员。最初与脂质代谢有关，最近发现该基因也参与生殖系干细胞中PIWI相互作用RNA的生物发生。为了研究其在癌症中皮尔纳代谢中的作用，在MDA-MB-231乳腺癌细胞中沉默该基因，并应用小RNA测序。PIWI相互作用的RNA和tRNA衍生片段表达谱显示GPAT 2沉默后的变化。有趣的是，在GPAT 2沉默的细胞中检测到两种小RNA的长度分布的显著变化。大多数下调的PIWI相互作用RNA在基因组中是单拷贝的，基因内的，在snoRNA中宿主，并且先前发现在癌细胞中上调。这些PIWI相互作用RNA的推定靶标与脂质代谢有关。下调的tRNA衍生片段来自所谓的“分化tRNA”，而上调的tRNA衍生片段来自增殖相关的tRNA。甘油-3-磷酸酰基转移酶-2沉默后miRNA量减少，对去调节的miRNA推定靶点的功能富集分析指向线粒体生物发生、IGF 1 R信号传导和脂质和脂蛋白的氧化代谢。此外，已知在预后不良的乳腺癌肿瘤中过表达的miRNA在GPAT 2沉默的细胞中被发现下调。总之，GPAT 2沉默定量和定性地影响PIWI相互作用RNA、tRNA衍生片段和miRNA的群体，其组合导致更分化的癌细胞表型。
Glycerol-3-phosphate acyltransferase-2 is a member of “cancer-testis gene” family. Initially linked to lipid metabolism, this gene has been recently found involved also in PIWI-interacting RNAs biogenesis in germline stem cells. To investigate its role in piRNA metabolism in cancer, the gene was silenced in MDA-MB-231 breast cancer cells and small RNA sequencing was applied. PIWI-interacting RNAs and tRNA-derived fragments expression profiles showed changes following GPAT2 silencing. Interestingly, a marked shift in length distribution for both small RNAs was detected in GPAT2-silenced cells. Most downregulated PIWI-interacting RNAs are single copy in the genome, intragenic, hosted in snoRNAs and previously found to be upregulated in cancer cells. Putative targets of these PIWI-interacting RNAs are linked to lipid metabolism. Downregulated tRNA derived fragments derived from, so-called ‘differentiation tRNAs’, whereas upregulated ones derived from proliferation-linked tRNAs. miRNA amounts decrease after Glycerol-3-phosphate acyltransferase-2 silencing and functional enrichment analysis of deregulated miRNA putative targets point to mitochondrial biogenesis, IGF1R signaling and oxidative metabolism of lipids and lipoproteins. In addition, miRNAs known to be overexpressed in breast cancer tumors with poor prognosis where found downregulated in GPAT2-silenced cells. In conclusion, GPAT2 silencing quantitatively and qualitatively affects the population of PIWI-interacting RNAs, tRNA derived fragments and miRNAs which, in combination, result in a more differentiated cancer cell phenotype.