Systematic Analysis of Gene Expression Alterations and Clinical Outcomes for Long-Chain Acyl-Coenzyme A Synthetase Family in Cancer.
Systematic Analysis of Gene Expression Alterations and Clinical Outcomes for Long-Chain Acyl-Coenzyme A Synthetase Family in Cancer.
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DOI：
10.1371/journal.pone.0155660
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Lai MD
中科院分区：
文献类型：
--
作者：
Chen WC;Wang CY;Hung YH;Weng TY;Yen MC;Lai MD
脂质代谢失调有助于癌症进展。我们以前的研究表明，长链脂肪酰辅酶A合成酶（ACSL）3是必需的内质网应激诱导的脂质上调。本研究旨在通过系统分析和体外实验研究ACSL家族在肿瘤中的作用。我们使用Oncomine数据库探索ACSL表达以确定癌发生过程中的基因改变，并使用PrognoScan数据库确定ACSL表达与癌症患者生存之间的关联。ACSL 1可能在结直肠癌和乳腺癌中发挥潜在的致癌作用，在肺癌中发挥潜在的抑癌作用。共表达分析显示ACSL 1在结肠癌中与MYBPH、PTPRE、PFKFB 3、SOCS 3共表达，在肺癌中与LRFIP 1、TSC 22 D1共表达。根据PrognoScan分析，结肠癌和乳腺癌细胞系中ACSL 1的下调抑制增殖、迁移和锚定非依赖性生长。相反，通过减弱ACSL 1，在肺癌细胞系中观察到致癌性增加。ACSL 3高表达预示卵巢癌预后较好;相反，ACSL 3高表达预示黑色素瘤预后较差。ACSL 3与SNUPN、TRIP 13和SEMA 5A在黑色素瘤中共表达。ACSL 4高表达预示结直肠癌预后较差，但预示乳腺癌、脑癌和肺癌预后较好。ACSL 4与SERPIN 2、HNRNPCL 1、ITIH 2、PROCR、LRFIP 1共表达。ACSL 5高表达预示乳腺癌、卵巢癌和肺癌预后良好。ACSL 5与TMEM 140、TAPBPL、BIRC 3、PTPRE和SERPINB 1共表达。ACSL 6水平低预示急性髓系白血病预后差。ACSL 6与SOX 6和DARC共表达。总之，ACSL的不同成员涉及不同类型的癌症发展。ACSL共表达分子可用于进一步研究ACSL家族在个体类型癌症中的作用。
Dysregulated lipid metabolism contributes to cancer progression. Our previous study indicates that long-chain fatty acyl-Co A synthetase (ACSL) 3 is essential for lipid upregulation induced by endoplasmic reticulum stress. In this report, we aimed to identify the role of ACSL family in cancer with systematic analysis and in vitro experiment. We explored the ACSL expression using Oncomine database to determine the gene alteration during carcinogenesis and identified the association between ACSL expression and the survival of cancer patient using PrognoScan database. ACSL1 may play a potential oncogenic role in colorectal and breast cancer and play a potential tumor suppressor role in lung cancer. Co-expression analysis revealed that ACSL1 was coexpressed with MYBPH, PTPRE, PFKFB3, SOCS3 in colon cancer and with LRRFIP1, TSC22D1 in lung cancer. In accordance with PrognoScan analysis, downregulation of ACSL1 in colon and breast cancer cell line inhibited proliferation, migration, and anchorage-independent growth. In contrast, increase of oncogenic property was observed in lung cancer cell line by attenuating ACSL1. High ACSL3 expression predicted a better prognosis in ovarian cancer; in contrast, high ACSL3 predicted a worse prognosis in melanoma. ACSL3 was coexpressed with SNUPN, TRIP13, and SEMA5A in melanoma. High expression of ACSL4 predicted a worse prognosis in colorectal cancer, but predicted better prognosis in breast, brain and lung cancer. ACSL4 was coexpressed with SERPIN2, HNRNPCL1, ITIH2, PROCR, LRRFIP1. High expression of ACSL5 predicted good prognosis in breast, ovarian, and lung cancers. ACSL5 was coexpressed with TMEM140, TAPBPL, BIRC3, PTPRE, and SERPINB1. Low ACSL6 predicted a worse prognosis in acute myeloid leukemia. ACSL6 was coexpressed with SOX6 and DARC. Altogether, different members of ACSLs are implicated in diverse types of cancer development. ACSL-coexpressed molecules may be used to further investigate the role of ACSL family in individual type of cancers.