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Cancer cells forgo translating mRNA transcribed from genes of nonspecialized tasks
FEBS Open Bio ( IF 2.6 ) Pub Date : 2024-03-12 , DOI: 10.1002/2211-5463.13787
Mahmoud Ahmed 1 , Trang Minh Pham 1 , Hyun Joon Kim 2 , Deok Ryong Kim 1
Affiliation  

The coupling of transcription and translation enables prokaryotes to regulate mRNA stability and reduce nonfunctional transcripts. Eukaryotes evolved other means to perform these functions. Here, we quantify the disparity between gene expression and protein levels and attempt to explain its origins. We collected publicly available simultaneous measurements of gene expression, protein level, division rate, and growth inhibition of breast cancer cells under drug perturbation. We used the cell lines as entities with shared origin, different evolutionary trajectories, and cancer hallmarks to define tasks subject to specializing and trading‐off. We observed varying average mRNA and protein correlation across cell lines, and it was consistently higher for the gene products in the cancer hallmarks. The enrichment of hallmark gene products signifies the resources invested in it as a task. Enrichment based on mRNA or protein abundance corresponds to the relative resources dedicated to transcription and translation. The differences in gene‐ and protein‐based enrichment correlated with nominal division rates but not growth inhibition under drug perturbations. Comparing the range of enrichment scores of the hallmarks within each cell signifies the resources dedicated to each. Cells appear to have a wider range of enrichment in protein synthesis relative to gene transcription. The difference and range of enrichment of the hallmark genes and proteins correlated with cell division and inhibition in response to drug treatments. We posit that cancer cells may express the genes coding for seemingly nonspecialized tasks but do not translate them to the corresponding proteins. This trade‐off may cost the cells under normal conditions but confer benefits during stress.

中文翻译:

癌细胞放弃翻译由非专业任务基因转录的 mRNA

转录和翻译的耦合使原核生物能够调节 mRNA 稳定性并减少非功能性转录物。真核生物进化出了其他方式来执行这些功能。在这里,我们量化了基因表达和蛋白质水平之间的差异,并试图解释其起源。我们收集了公开的同步测量数据,测量药物干扰下乳腺癌细胞的基因表达、蛋白质水平、分裂率和生长抑制。我们使用细胞系作为具有共同起源、不同进化轨迹和癌症标志的实体来定义需要专业化和权衡的任务。我们观察到不同细胞系的平均 mRNA 和蛋白质相关性不同,并且癌症标志中的基因产物的相关性始终较高。标志性基因产物的富集意味着作为一项任务投入的资源。基于 mRNA 或蛋白质丰度的富集对应于专用于转录和翻译的相关资源。基于基因和蛋白质的富集差异与名义分裂率相关,但与药物扰动下的生长抑制无关。比较每个单元内标志的富集分数范围意味着专用于每个单元的资源。相对于基因转录,细胞的蛋白质合成似乎具有更广泛的富集范围。标志基因和蛋白质富集的差异和范围与药物治疗反应的细胞分裂和抑制相关。我们假设癌细胞可能表达编码看似非专门任务的基因,但不会将它们翻译成相应的蛋白质。这种权衡可能会在正常条件下使细胞付出代价,但在压力下却会带来好处。
更新日期:2024-03-12
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