尽管在动态肿瘤微环境中复杂基因调控机制方面取得了很大的进展，但长链非编码RNA（lncRNA）在癌细胞代谢中的潜在贡献尚不清楚。死亡受体5反义（DR5-AS）是一种顺铂诱导的lncRNA，其敲低调节细胞形态，但其对细胞代谢的影响尚不清楚。本研究的目的是检测顺铂和DR5-AS lncRNA在HeLa细胞中调节的代谢变化。我们使用顺铂作为普遍的抗癌药物，在HeLa宫颈癌细胞中调节代谢变化。然后，我们通过傅立叶红外光谱（FTIR）检测了代谢变化的程度。我们还通过用顺铂处理的HeLa细胞中分离的总RNA产生新的RNA-seq数据进行转录组学分析。然后，我们将顺铂介导的转录组学变化和大分子变化与DR5-AS敲低介导的变化进行了比较。顺铂处理导致不饱和脂肪酸和脂质与蛋白质比例以及甘露醇含量的变化。这些观察到的细胞代谢变化得到了转录组学分析的支持。FTIR光谱分析揭示，DR5-AS敲低导致脂质/蛋白质比例增加了20.9%，脂质过氧化物减少了76.6%。此外，我们检测到脂肪族脂质链长增加了3.42%，RNA含量增加，甘露醇含量减少，表明DR5-AS敲低的HeLa细胞的代谢活性相对较低。有趣的是，在顺铂处理和DR5-AS敲低的HeLa细胞中观察到类似的基因表达模式。这些结果表明，在HeLa宫颈癌细胞中，DR5-AS lncRNA可能解释了顺铂介导的大分子和代谢变化的一部分。© TÜBİTAK.

Despite great progress in complex gene regulatory mechanisms in the dynamic tumor microenvironment, the potential contribution of long noncoding RNAs (lncRNAs) to cancer cell metabolism is poorly understood. Death receptor 5 antisense (DR5-AS) is a cisplatin inducible lncRNA whose knockdown modulates cell morphology. However, its effect on cell metabolism is unknown. The aim of this study is to examine metabolic changes modulated by cisplatin and DR5-AS lncRNA in HeLa cells.We used cisplatin as a universal cancer therapeutic drug to modulate metabolic changes in HeLa cervix cancer cells. We then examined the extent of metabolic changes by Fourier transform infrared spectroscopy (FTIR). We also performed transcriptomics analyses by generating new RNA-seq data with total RNAs isolated from cisplatin-treated HeLa cells. Then, we compared cisplatin-mediated transcriptomics and macromolecular changes with those mediated by DR5-AS knockdown.Cisplatin treatment caused changes in the unsaturated fatty acid and lipid-to-protein ratios and the glycogen content. These observations in altered cellular metabolism were supported by transcriptomics analyses. FTIR spectroscopy analyses have revealed that DR5-AS knockdown causes a 20.9% elevation in the lipid/protein ratio and a 76.6% decrease in lipid peroxidation. Furthermore, we detected a 3.42% increase in the chain length of the aliphatic lipids, a higher content of RNA, and a lower amount of glycogen indicating relatively lower metabolic activity in the DR5-AS knockdown HeLa cells. Interestingly, we observed a similar gene expression pattern under cisplatin treatment and DR5-AS knockdown HeLa cells.These results suggest that DR5-AS lncRNA appears to account for a fraction of cisplatin-mediated macromolecular and metabolic changes in HeLa cervix cancer cells.© TÜBİTAK.