Azzam Hany N, El-Derany Marwa O, Wahdan Sara A, Faheim Reham M, Helal Gouda K, El-Demerdash Ebtehal
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt.
Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Hum Cell. 2023 Nov;36(6):1877-1886. doi: 10.1007/s13577-023-00977-5. Epub 2023 Aug 30.
Only a few investigations, to our knowledge, have examined the bioenergetics of Tamoxifen (TMX) resistant individuals and reported altered mitochondrial activity and metabolic profile. The primary cause of TMX resistance is firmly suggested to be metabolic changes. Metabolic variations and hypoxia have also been linked in a bidirectional manner. Increased hypoxic levels correlate with early recurrence and proliferation and have a negative therapeutic impact on breast cancer (BC) patients. Hypoxia, carcinogenesis, and patient death are all correlated, resulting in more aggressive traits, a higher chance of metastasis, and TMX resistance. Consequently, we sought to investigate the possible role of the metabolic/hypoxial axis Long non-coding RNA (LncRNA) Taurine up-regulated 1 (TUG-1), Micro-RNA 186-5p (miR-186), Sirtuin-3 (SIRT3), Peroxisome Proliferator Activator Receptor alpha (PPAR-α), and Hypoxia-Inducible Factor-1 (HIF-1) in the development of TMX resistance in BC patients and to correlate this axis with tumor progression. Interestingly, this will be the first time to explore epigenetic regulation of this axis in BC.
据我们所知，仅有少数研究对他莫昔芬（TMX）耐药个体的生物能量学进行了研究，并报告了线粒体活性和代谢谱的改变。强烈提示TMX耐药的主要原因是代谢变化。代谢变化与缺氧也以双向方式相关联。缺氧水平升高与早期复发和增殖相关，并对乳腺癌（BC）患者产生负面治疗影响。缺氧、致癌作用和患者死亡均相互关联，导致更具侵袭性的特征、更高的转移几率和TMX耐药性。因此，我们试图研究代谢/缺氧轴长链非编码RNA（LncRNA）牛磺酸上调1（TUG-1）、微小RNA 186-5p（miR-186）、沉默调节蛋白3（SIRT3）、过氧化物酶体增殖物激活受体α（PPAR-α）和缺氧诱导因子-1（HIF-1）在BC患者TMX耐药发展中的可能作用，并将该轴与肿瘤进展相关联。有趣的是，这将是首次在BC中探索该轴的表观遗传调控。
