Lysophosphatidylcholine acyltransferase 1 upregulation and concomitant phospholipid alterations in clear cell renal cell carcinoma.
Lysophosphatidylcholine acyltransferase 1 upregulation and concomitant phospholipid alterations in clear cell renal cell carcinoma.
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DOI：
10.1186/s13046-017-0525-1
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发表时间：
2017-05-12
期刊：
影响因子：
--
通讯作者：
Xu T
中科院分区：
文献类型：
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作者：
Du Y;Wang Q;Zhang X;Wang X;Qin C;Sheng Z;Yin H;Jiang C;Li J;Xu T
据报道，脂质代谢参与肿瘤发生和透明细胞肾细胞癌（ccRCC）的进展。然而，磷脂谱改变在 ccRCC 中的作用尚未得到系统探索。在本研究中，我们比较了 ccRCC 和配对正常肾组织之间的磷脂组成。使用液相色谱串联质谱法 (LC/MS/MS) 评估配对 ccRCC 和正常肾组织的磷脂组成。为了评估将溶血磷脂酰胆碱 (LPC) 转化为磷脂酰胆碱 (PC) 的溶血磷脂酰胆碱酰基转移酶 (LPCAT) 的 mRNA 和蛋白质水平，进行了 qRT-PCR、蛋白质印迹和免疫组织化学分析。评估LPCAT1表达与临床病理特征和预后的相关性。此外，使用siRNA敲低ccRCC细胞系中LPCAT1的表达，并研究其对细胞增殖、细胞周期、迁移和侵袭的影响。 ccRCC与正常肾组织的磷脂组成存在显着差异。癌组织中多种LPC种类减少，相应的PC种类增加。与正常肾组织相比，ccRCC组织中LPCAT1的mRNA和蛋白水平上调，并且LPCAT1表达与不良病理特征（较高的肿瘤分级、较高的TNM分期和较大的肿瘤尺寸）和总生存显着相关。在细胞系实验中，LPCAT1 敲低会耗尽 PC，抑制细胞增殖、迁移和侵袭，并诱导细胞周期停滞在 G0/G1 期。在 ccRCC 组织中观察到 PC 和 LPC 组成的选择性变化。 LPCAT1 的过度表达可能通过 LPC 向 PC 的转化促进 ccRCC 的发生和进展。本文的在线版本 (doi:10.1186/s13046-017-0525-1) 包含补充材料，可供授权用户使用。
The involvement of lipid metabolism in tumourigenesis and the progression of clear cell renal cell carcinoma (ccRCC) have been reported. However, the role of phospholipid profile alterations in ccRCC has not yet been systematically explored. In the present study, we compared the phospholipid compositions between ccRCC and paired normal renal tissues. The phospholipid compositions of paired ccRCC and normal renal tissues were evaluated using liquid chromatography tandem mass spectrometry (LC/MS/MS). To evaluate the mRNA and protein levels of lysophosphatidylcholine acyltransferase (LPCAT), which converts lysophosphatidylcholine (LPC) to phosphatidylcholine (PC), qRT-PCR, western blotting and immunohistochemistry were performed. The correlations of LPCAT1 expression with clinicopathological features and prognosis were assessed. In addition, siRNAs were used to knockdown LPCAT1 expression in ccRCC cell lines, and its effect on cell proliferation, cell cycle, migration and invasion were investigated. The phospholipid compositions of ccRCC and normal renal tissues were significantly different. Multiple LPC species were decreased and corresponding PC species were increased in cancer tissues. The mRNA and protein levels of LPCAT1 were up-regulated in ccRCC tissues compared with normal renal tissues, and LPCAT1 expression was significantly correlated with unfavourable pathological features (higher tumour grade, higher TNM stage and larger tumour size) and overall survival. In cell line experiments, LPCAT1 knockdown depleted PCs, inhibited cell proliferation, migration and invasion and induced cell cycle arrest at the G0/G1 phase. Selective changes in PC and LPC composition were observed in ccRCC tissues. The overexpression of LPCAT1 promotes the development and progression of ccRCC, likely through the conversion of LPC to PC. The online version of this article (doi:10.1186/s13046-017-0525-1) contains supplementary material, which is available to authorized users.