Multiomics analysis of metabolic heterogeneity in cervical cancer cell lines with or without HPV.
Multiomics analysis of metabolic heterogeneity in cervical cancer cell lines with or without HPV.
复制标题
DOI：
10.3389/fonc.2023.1194462
复制
发表时间：
2023
影响因子：
4.7
通讯作者：
Chen, Xiaohua
中科院分区：
文献类型：
--
作者：
Liu, Xu;Zhu, Yaqi;Huang, Sheng;Shi, Tingyu;Li, Tanghua;Lan, Yanan;Cao, Xiaojian;Wu, Yingtao;Ding, Jinya;Chen, Xiaohua
代谢组学分析揭示了宫颈癌细胞C33 A和CaSki的代谢异质性，并探讨了其分子机制。用改良的Bligh-Dyer法将C33 A和CaSki细胞内源性代谢产物分为极性和非极性组分。通过超高效液相色谱-四极杆-飞行时间质谱法（UPLC-Q-TOF-MS）分析代谢产物。然后，结合多元统计分析和火山图筛选差异代谢产物，并对差异代谢产物进行功能富集和途径分析。最后，结合转录组学进行关联分析，并通过实时PCR（RT-qPCR）和油红染色实验验证了重要的差异代谢。结果表明，C33 A和CaSki细胞在代谢途径中的氨基酸、核苷酸和脂类，如苏氨酸、花生四烯酸和次黄嘌呤等存在显著差异。这些化合物可用作细胞代谢差异的标志物。脂质代谢的异质性占87.8%，其中C33 A细胞表现出较高的脂肪酸极性衍生物含量，而CaSki细胞表现出较高的游离脂肪酸和甘油酯含量。基于上述HPV途径中代谢差异以及脂质代谢相关基因的相关性分析，p53和脂质代谢途径中涉及的基因，如过氧化物酶体激活受体γ（PPARG）和硬脂酰辅酶A去饱和酶（SCD），与细胞的代谢异质性相关。通过RT-qPCR验证了一些基因的差异表达。CaSki细胞显示出显著高于C33 A细胞的甘油酯水平，如通过油红O染色和甘油酯测定所证实的。以上结果表明，C33 A和CaSki细胞的代谢组学差异比较明显，尤其是在脂质代谢方面，可能与HPV E6导致PPARG和p53表达降低有关。深入研究HPV感染与非感染宫颈癌细胞系脂质代谢异质性的分子机制，可为宫颈癌细胞系的开发和肿瘤患者的个体化治疗提供新的参考。
Metabolomics analysis revealed the metabolic heterogeneity of cervical cancer (CC) cell lines C33A and CaSki, and their molecular mechanisms were explored. Using the modified Bligh-Dyer method, the endogenous metabolites of C33A and CaSki cells were divided into polar and nonpolar fractions. The metabolites were analysed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Then, the differential metabolites were screened by combining multivariate statistical analysis and volcano maps, and functional enrichment and pathway analysis of the differential metabolites were performed. Finally, association analysis was carried out in combination with transcriptomics, and the important differential metabolisms were experimentally verified by real-time PCR (RT−qPCR) and oil red staining. The results showed that between the C33A and CaSki cell lines, there were significant differences in amino acids, nucleotides and lipids, such as in threonine, arachidonic acid and hypoxanthine, in the metabolic pathways. These compounds could be used as markers of differences in cellular metabolism. The heterogeneity of lipid metabolism accounted for 87.8%, among which C33A cells exhibited higher contents of fatty acid polar derivatives, while CaSki cells showed higher contents of free fatty acids and glycerides. Based on correlation analysis of the above metabolic differences in HPV pathways as well as lipid metabolism-related genes, p53 and the genes involved in lipid metabolism pathways, such as Peroxisome Proliferator Activated Receptor Gamma(PPARG) and stearoyl-CoA desaturase (SCD), are relevant to the metabolic heterogeneity of the cells. The differential expression of some genes was validated by RT−qPCR. CaSki cells showed significantly higher glyceride levels than that of C33A cells, as verified by oil red O staining and glyceride assays. The above results showed that the metabolomic differences between C33A and CaSki cells were relatively obvious, especially in lipid metabolism, which might be related to the decreased expression of PPARG and p53 caused by HPV E6. Further studies on the molecular mechanism of lipid metabolism heterogeneity in cervical cancer cell lines with or without HPV could provide a new reference for the development of CC and individualized treatments of tumour patients.
登录
查看更多内容
影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
4.6
作者：
Pappa KI;Daskalakis G;Anagnou NP
通讯作者：
Anagnou NP
DOI：
10.1016/j.bbrc.2018.02.097
发表时间：
2018-10-07
影响因子：
3.1
作者：
Maan M;Peters JM;Dutta M;Patterson AD
通讯作者：
Patterson AD
影响因子：
29
作者：
Cheng, Xiang;Geng, Feng;Guo, Deliang
通讯作者：
Guo, Deliang
影响因子：
1.7
作者：
Kechin, Andrey;Boyarskikh, Uljana;Filipenko, Maxim
通讯作者：
Filipenko, Maxim