Metabolomics study reveals the potential evidence of metabolic reprogramming towards the Warburg effect in precancerous lesions.
Metabolomics study reveals the potential evidence of metabolic reprogramming towards the Warburg effect in precancerous lesions.
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代谢组学研究揭示了癌前病变中代谢重编程对 Warburg 效应的潜在证据
DOI：
10.7150/jca.54252
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发表时间：
2021
影响因子：
3.9
通讯作者：
Yu D
中科院分区：
文献类型：
--
作者：
Chen X;Yi C;Yang MJ;Sun X;Liu X;Ma H;Li Y;Li H;Wang C;He Y;Chen G;Chen S;Yu L;Yu D
背景：即使有氧，大多数肿瘤的糖酵解通量也会增强，称为有氧糖酵解或 Warburg 效应。代谢重编程促进癌症进展，甚至与肿瘤发生有关。然而，尚不清楚观察到的代谢变化是癌症发展的驱动因素还是旁观者。方法：本研究通过代谢组学分析口腔癌前细胞和宫颈癌前病变的代谢特征，并通过RT-PCR和Western blot分析评估宫颈癌前病变中糖酵解酶的表达情况。结果：总共在口腔细胞和宫颈组织中分别鉴定出 115 种和 23 种具有可靠信号的代谢物。根据代谢组，口腔癌前细胞DOK可以与正常人口腔上皮细胞（HOEC）和口腔癌细胞清楚地区分。在 DOK 和 HOEC 之间确定了四种关键的差异代谢物（丙酮酸、谷氨酰胺、蛋氨酸和赖氨酸）。代谢特征可以清楚地区分宫颈癌前病变、正常宫颈上皮和宫颈癌。与正常宫颈上皮相比，宫颈癌前病变的葡萄糖消耗和乳酸产生增加。宫颈癌前病变中糖酵解酶LDHA、HK II、PKM2的表达较正常宫颈上皮呈升高趋势。结论：我们的研究结果表明，细胞代谢可能在肿瘤发生的早期进行重编程，这意味着代谢重编程对肿瘤的发展做出了贡献。
Background: Most tumors have an enhanced glycolysis flux, even when oxygen is available, called the aerobic glycolysis or the Warburg effect. Metabolic reprogramming promotes cancer progression, and is even related to the tumorigenesis. However, it is not clear whether the observed metabolic changes act as a driver or a bystander in cancer development. Methods: In this study, the metabolic characteristics of oral precancerous cells and cervical precancerous lesions were analyzed by metabolomics, and the expression of glycolytic enzymes in cervical precancerous lesions was evaluated by RT-PCR and Western blot analysis. Results: In total, 115 and 23 metabolites with reliable signals were identified in oral cells and cervical tissues, respectively. Based on the metabolome, oral precancerous cell DOK could be clearly separated from normal human oral epithelial cells (HOEC) and oral cancer cells. Four critical differential metabolites (pyruvate, glutamine, methionine and lysine) were identified between DOK and HOEC. Metabolic profiles could clearly distinguish cervical precancerous lesions from normal cervical epithelium and cervical cancer. Compared with normal cervical epithelium, the glucose consumption and lactate production increased in cervical precancerous lesions. The expression of glycolytic enzymes LDHA, HK II and PKM2 showed an increased tendency in cervical precancerous lesions compared with normal cervical epithelium. Conclusions: Our findings suggest that cell metabolism may be reprogrammed at the early stage of tumorigenesis, implying the contribution of metabolic reprogramming to the development of tumor.
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影响因子：
29
作者：
Pavlova NN;Thompson CB
通讯作者：
Thompson CB
影响因子：
21.3
作者：
Cox AG;Hwang KL;Brown KK;Evason K;Beltz S;Tsomides A;O'Connor K;Galli GG;Yimlamai D;Chhangawala S;Yuan M;Lien EC;Wucherpfennig J;Nissim S;Minami A;Cohen DE;Camargo FD;Asara JM;Houvras Y;Stainier DYR;Goessling W
通讯作者：
Goessling W
影响因子：
82.9
作者：
Wang, Zhenxun;Yip, Lian Yee;Tam, Wai Leong
通讯作者：
Tam, Wai Leong
DOI：
10.1093/bioinformatics/bty528
发表时间：
2018-12-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Chong J;Xia J
通讯作者：
Xia J
影响因子：
64.8
作者：
Gao, Xia;Sanderson, Sydney M.;Locasale, Jason W.
通讯作者：
Locasale, Jason W.