Sun Yifeng, Xu Zhao, Jiang Jifeng, Xu Tianhong, Xu Jiadai, Liu Peng
Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China.
Front Oncol. 2020 Sep 10;10:563666. doi: 10.3389/fonc.2020.563666. eCollection 2020.
Most patients with multiple myeloma (MM) will eventually relapse and current treatments have limited effect. Herein, we demonstrate that succinate dehydrogenase subunit A (SDHA) was low expressed in MM patients, and patients with SDHA relatively high expression had long overall survival and progression-free survival. Furthermore, SDHA high expression inhibited proliferation and invasion in MM cell lines and enhanced the anti-tumor and synergistic effect of chemotherapeutics. More importantly, chidamide was proved effective in MM by targeting SDHA, and expression of SDHA was increased by chidamide through acetylating H3K27 site of SDHA. Collectively, high expression of SDHA, which was regulated by histone acetylation and targeted by chidamide, might become a good prognostic factor of MM patients.
大多数多发性骨髓瘤(MM)患者最终会复发,且目前的治疗效果有限。在此,我们证明琥珀酸脱氢酶亚基A(SDHA)在MM患者中低表达,SDHA相对高表达的患者总生存期和无进展生存期较长。此外,SDHA高表达抑制MM细胞系的增殖和侵袭,并增强化疗药物的抗肿瘤和协同作用。更重要的是,西达本胺通过靶向SDHA被证明对MM有效,且西达本胺通过乙酰化SDHA的H3K27位点增加SDHA的表达。总体而言,受组蛋白乙酰化调节且被西达本胺靶向的SDHA高表达可能成为MM患者的良好预后因素。