High Expression of Succinate Dehydrogenase Subunit A Which Is Regulated by Histone Acetylation, Acts as a Good Prognostic Factor of Multiple Myeloma Patients.

Yifeng Sun,Peng Liu,Jiadai Xu,Jifeng Jiang,Tianhong Xu,Zhao Xu

doi:10.3389/fonc.2020.563666

Abstract

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.

Highlights

Multiple myeloma (MM) is a common hematological malignancy characterized by proliferation of monoclonal malignant plasma cells and production of monoclonal immunoglobulin [1]
Western blot analysis showed that only chidamide increased the expression of SDHA, whereas expression of SDHA stayed at the same level in bortezomib and lenalidomide treated cells compared with control (Supplementary Figure S1A)
To determine the effect of regular histone deacetylase inhibitor (HDACi) on regulating SDHA, we tested the expression of SDHA in MM cell lines by real-time RT-PCR after treating with three kinds of HDACi, including valproic acid (VPA), vorinostat (SAHA) and chidamide

Summary

Introduction

Multiple myeloma (MM) is a common hematological malignancy characterized by proliferation of monoclonal malignant plasma cells and production of monoclonal immunoglobulin [1]. Durie/Salmon (DS) staging system is depended on concentration of hemoglobin and serum calcium, the number of osteolytic lesions and production of serum immunoglobulin and urine Bence Jones protein [5]. In 2015, on the basis of ISS staging system, International Myeloma Working Group (IMWG) added molecular genetic abnormality and level of lactate dehydrogenase (LDH) in the system, which was named as Revised International Staging System (R-ISS) [7]. These staging systems were regarded as common prognostic criteria of MM patients

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