Multi-Omics Analysis of Fatty Acid Metabolism in Thyroid Carcinoma.
Multi-Omics Analysis of Fatty Acid Metabolism in Thyroid Carcinoma.
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DOI：
10.3389/fonc.2021.737127
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发表时间：
2021
影响因子：
4.7
通讯作者：
Yue X
中科院分区：
文献类型：
--
作者：
Lu J;Zhang Y;Sun M;Ding C;Zhang L;Kong Y;Cai M;Miccoli P;Ma C;Yue X
甲状腺乳头状癌（PTC）占甲状腺癌的大多数，并影响大量的个体。PTC的发病机制至今尚未完全阐明。代谢重编程是肿瘤的一个常见特征。我们以前的研究揭示了PTC中脂质代谢的重编程。进一步研究脂质代谢重编程可能有助于阐明PTC的发病机制。使用脂质组学、蛋白质组学和代谢组学方法分析PTC和肿瘤旁组织的临床样本。采用多组学整合策略，以确定PTC的重要途径。这些发现进一步证实了使用蛋白质印迹，组织芯片，生物信息学，细胞迁移试验。多组学数据和综合分析的结果表明，脂肪酸代谢的三个步骤（水解，运输和氧化）在PTC中显着增强。特别是，LPL，FATP 2和CPT 1A的表达水平，在各自的步骤中的三个关键酶，在PTC中升高。LPL、FATP 2和CPT 1A的表达与PTC的TNM分期、淋巴结转移有关。高水平的FATP 2和CPT 1A与PTC预后不良有关。此外，LPL、FATP 2和CPT 1A的异位过表达可各自促进甲状腺癌细胞的迁移。我们的数据表明，增强脂肪酸代谢提供了额外的能量和底物PTC的进展。这可能有助于阐明PTC的发病机制，并确定潜在的治疗PTC的目标。
Papillary thyroid carcinoma (PTC) accounts for the majority of thyroid cancer and affects a large number of individuals. The pathogenesis of PTC has not been completely elucidated thus far. Metabolic reprogramming is a common feature in tumours. Our previous research revealed the reprogramming of lipid metabolism in PTC. Further studies on lipid metabolism reprogramming may help elucidate the pathogenesis of PTC. Clinical samples of PTC and para-tumour tissue were analysed using lipidomic, proteomic, and metabolomic approaches. A multi-omics integrative strategy was adopted to identify the important pathways in PTC. The findings were further confirmed using western blotting, tissue microarray, bioinformatics, and cell migration assays. Multi-omics data and the results of integrated analysis revealed that the three steps of fatty acid metabolism (hydrolysis, transportation, and oxidation) were significantly enhanced in PTC. Especially, the expression levels of LPL, FATP2, and CPT1A, three key enzymes in the respective steps, were elevated in PTC. Moreover, LPL, FATP2 and CPT1A expression was associated with the TNM stage, lymph node metastasis of PTC. Moreover, high levels of FATP2 and CPT1A contributed to poor prognosis of PTC. In addition, ectopic overexpression of LPL, FATP2 and CPT1A can each promote the migration of thyroid cancer cells. Our data suggested that enhanced fatty acid metabolism supplied additional energy and substrates for PTC progression. This may help elucidating the underlying mechanism of PTC pathogenesis and identifying the potential therapeutic targets for PTC.
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影响因子：
5.7
作者：
Kuemmerle NB;Rysman E;Lombardo PS;Flanagan AJ;Lipe BC;Wells WA;Pettus JR;Froehlich HM;Memoli VA;Morganelli PM;Swinnen JV;Timmerman LA;Chaychi L;Fricano CJ;Eisenberg BL;Coleman WB;Kinlaw WB
通讯作者：
Kinlaw WB
影响因子：
3.5
作者：
Heinzer, AK;Watkins, PA;Smith, KD
通讯作者：
Smith, KD
DOI：
10.1186/s40880-018-0301-4
发表时间：
2018-05-21
期刊：
Cancer communications (London, England)
影响因子：
--
作者：
Cheng C;Geng F;Cheng X;Guo D
通讯作者：
Guo D
影响因子：
11.8
作者：
Hoffman, Kate;Lorenzo, Amelia;Sosa, Julie Ann
通讯作者：
Sosa, Julie Ann
影响因子：
11.2
作者：
Migita, Toshiro;Narita, Tadahito;Ishikawa, Yuichi
通讯作者：
Ishikawa, Yuichi