Orre Charlotte, Dieu Xavier, Guillon Jordan, Gueguen Naïg, Ahmadpour Seyedeh Tayebeh, Dumas Jean-François, Khiati Salim, Reynier Pascal, Lenaers Guy, Coqueret Olivier, Chevrollier Arnaud, Mirebeau-Prunier Delphine, Desquiret-Dumas Valérie
Mitolab Team, Inserm U1083, CNRS 6015, Mito Vasc Institute, SFR ICAT, Angers University, F-49000 Angers, France.
Service de Biochimie et Biologie Moléculaire, CHU Angers, F-49933 Angers, France.
Biology (Basel). 2021 Nov 9;10(11):1156. doi: 10.3390/biology10111156.
Despite improvements in therapeutic strategies for treating breast cancers, tumor relapse and chemoresistance remain major issues in patient outcomes. Indeed, cancer cells display a metabolic plasticity allowing a quick adaptation to the tumoral microenvironment and to cellular stresses induced by chemotherapy. Recently, long non-coding RNA molecules (lncRNAs) have emerged as important regulators of cellular metabolic orientation. In the present study, we addressed the role of the long non-coding RNA molecule (lncRNA) SAMMSON on the metabolic reprogramming and chemoresistance of MCF-7 breast cancer cells resistant to doxorubicin (MCF-7dox). Our results showed an overexpression of SAMMSON in MCF-7dox compared to doxorubicin-sensitive cells (MCF-7). Silencing of SAMMSON expression by siRNA in MCF-7dox cells resulted in a metabolic rewiring with improvement of oxidative metabolism, decreased mitochondrial ROS production, increased mitochondrial replication, transcription and translation and an attenuation of chemoresistance. These results highlight the role of SAMMSON in the metabolic adaptations leading to the development of chemoresistance in breast cancer cells. Thus, targeting SAMMSON expression levels represents a promising therapeutic route to circumvent doxorubicin resistance in breast cancers.
尽管乳腺癌治疗策略有所改进，但肿瘤复发和化疗耐药仍是影响患者预后的主要问题。事实上，癌细胞表现出代谢可塑性，能够快速适应肿瘤微环境以及化疗诱导的细胞应激。最近，长链非编码RNA分子（lncRNAs）已成为细胞代谢方向的重要调节因子。在本研究中，我们探讨了长链非编码RNA分子（lncRNA）SAMMSON对耐阿霉素的MCF-7乳腺癌细胞（MCF-7dox）代谢重编程和化疗耐药的作用。我们的结果显示，与阿霉素敏感细胞（MCF-7）相比，SAMMSON在MCF-7dox中过表达。在MCF-7dox细胞中通过siRNA沉默SAMMSON表达导致代谢重塑，氧化代谢改善，线粒体ROS产生减少，线粒体复制、转录和翻译增加，化疗耐药性减弱。这些结果突出了SAMMSON在导致乳腺癌细胞化疗耐药性发展的代谢适应中的作用。因此，靶向SAMMSON表达水平代表了一种有前景的治疗途径，以规避乳腺癌中的阿霉素耐药性。
