LncRNA HCG11 regulates selinexor sensitivity in multiple myeloma

  • Biochem Pharmacol. 2025 Jul:237:116948. doi: 10.1016/j.bcp.2025.116948.
Yue Zhang  1 ,  Xin Wang  1 ,  Hongmei Luo  1 ,  Xiang Liu  1 ,  Jingcao Huang  1 ,  Ziyue Mi  1 ,  Siyao He  1 ,  Jingjing Wen  2 ,  Qianwen Gao  3 ,  Haonan Yang  1 ,  Yu Feng  1 ,  Linfeng Li  1 ,  Xinyu Zhai  1 ,  Fangfang Wang  1 ,  Yang Dai  1 ,  Li Zhang  1 ,  Ting Niu  1 ,  Chunyan Sun  4 ,  Yuhuan Zheng  5
Affiliations
  • 1. Department of Hematology/Institute of Hematology Research, West China Hospital, Sichuan University, Chengdu, China.
  • 2. Department of Hematology/Institute of Hematology Research, West China Hospital, Sichuan University, Chengdu, China; Department of Hematology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China.
  • 3. Department of Hematology/Institute of Hematology Research, West China Hospital, Sichuan University, Chengdu, China; College of Life Science, Sichuan University, Chengdu, China.
  • 4. Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China. Electronic address: [email protected].
  • 5. Department of Hematology/Institute of Hematology Research, West China Hospital, Sichuan University, Chengdu, China. Electronic address: [email protected].
PMID: 40228640 DOI: 10.1016/j.bcp.2025.116948
Abstract

Multiple myeloma (MM) is an incurable plasma cell caner featured by monoclonal plasma cell proliferation in bone marrow. The patients inevitably encounter drug resistance and the Cancer relapse. Selinexor, a selective inhibitor of nuclear export by targeting exportin-1 (XPO1), is a novel medication in MM treatment. However, there were still many MM patients who did not respond to selinexor without mechanisms being fully demonstrated. In this study, we found that a long noncoding RNA (lncRNA), HLA complex Group 11 (HCG11), regulated MM cell growth and sensitivity to selinexor. MM cell lines and primary MM cell expressed HCG11. High HCG11 expression in MM correlated with inferior patients' overall survival. HCG11 knockdown (HCG11-KD) MM cells were more sensitive to selinexor-induced Apoptosis. Mechanistically, HCG11 bound to XPO1 mRNA and promoted the mRNA stability and translation in cells. Thus, HCG11-KD MM cells had reduced XPO1 expression. Animal study showed that HCG11-KD MM was more sensitivity to selinexor than control knockdown in vivo. Overall, our study suggested a regulation of selinexor sensitivity in MM by lncRNA HCG11.

Keywords
HCG11; LncRNA; Multiple myeloma; Selinexor.
Products