Despite considerable efforts in prevention and therapy, breast cancer remains a major public health concern worldwide. Numerous studies using breast cancer cell lines have shown the antiproliferative and pro-apoptotic effects of docosahexaenoic acid (DHA). Some studies have also demonstrated the inhibitory effect of DHA on the migration and invasion of breast cancer cells, making DHA a potential anti-metastatic agent. Thus, DHA has shown its potential as a chemotherapeutic adjuvant. However, the molecular mechanisms triggering DHA effects remain unclear, and the aim of this study was to provide a transcriptomic basis for further cellular and molecular investigations. Therefore, MDA-MB-231 cells were treated with 100 µM DHA for 1`2 h or 24 h before RNA-seq analysis. The results show the great impact of DHA-treatment on the transcriptome, especially after 24 h of treatment. The impact of DHA is particularly visible in genes involved in the cholesterol biosynthesis pathway that is strongly downregulated, and the endoplasmic reticulum (ER)-stress response that is, conversely, upregulated. This ER-stress and unfolded protein response could explain the pro-apoptotic effect of DHA. The expression of genes related to migration and invasion (especially SERPINE1, PLAT, and MMP11) is also impacted by DHA. In conclusion, this transcriptomic analysis supports the antiproliferative, pro-apoptotic and anti-invasive effects of DHA, and provides new avenues for understanding its molecular mechanisms.

中文翻译：

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乳腺癌细胞MDA-MB-231对二十二碳六烯酸的转录反应：脂质和胆固醇代谢基因的下调和促凋亡ER-Stress通路的基因的上调。

尽管在预防和治疗方面做出了巨大努力，但是乳腺癌仍然是全世界主要的公共卫生问题。使用乳腺癌细胞系的大量研究表明二十二碳六烯酸（DHA）具有抗增殖和促凋亡作用。一些研究还证明了DHA对乳腺癌细胞迁移和侵袭的抑制作用，使DHA成为潜在的抗转移剂。因此，DHA已显示出其作为化学治疗佐剂的潜力。但是，触发DHA效应的分子机制仍不清楚，本研究的目的是为进一步的细胞和分子研究提供转录组学基础。因此，在进行RNA序列分析之前，将MDA-MB-231细胞用100 µM DHA处理1`2 h或24 h。结果表明DHA处理对转录组有很大影响，特别是治疗24小时后。DHA的影响在与胆固醇生物合成途径有关的基因中强烈下调，而与内质网（ER）应激反应相反（上调）。这种内质网应激和未折叠的蛋白质反应可以解释DHA的促凋亡作用。与迁移和入侵有关的基因的表达（尤其是SERPINE1，PLAT和MMP11）也受到DHA的影响。总之，该转录组学分析支持DHA的抗增殖，促凋亡和抗侵袭作用，并为了解其分子机制提供了新途径。