Research Paper Volume 14, Issue 19 pp 7972—7985

DAZAP1 facilitates the alternative splicing of KITLG to promote multiple myeloma cell proliferation via ERK signaling pathway

Yanyan Zhou1,2, *, , Shaohua Huangfu1, *, , Muxi Li3, *, , Chao Tang2, , Jinjun Qian2, , Mengjie Guo2, , Zuojian Zhou4, , Ye Yang2, , Chunyan Gu1,2, ,

  • 1 Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
  • 2 School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
  • 3 School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
  • 4 College of Artifical Intelligence and Information Technology, Nanjing University of Chinese Medicine, Nanjing, China
* Co-first author

Received: June 24, 2022       Accepted: September 23, 2022       Published: October 13, 2022
How to Cite

Copyright: © 2022 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Multiple myeloma (MM) is an incurable plasma cell malignancy, in which alternative pre-mRNA splicing (AS) acts as one of the key transcriptome modifier. The Deleted in Azoospermia-Associated Protein 1 (DAZAP1) is a splicing factor that has been identified as an oncogene in multiple cancers, yet its role in MM proliferation remains unclear. We first analyzed MM clinical databases and found that MM patients with elevated DAZAP1 had a poor survival. Furthermore, we overexpressed DAZAP1 by lentiviral transfection and utilized siRNA silencing the expression of DAZAP1 in MM cells. DAZAP1 promoted MM cell proliferation in vitro and accelerated MM xenograft tumor growth in vivo. KEGG pathway enrichment analysis showed that ERK signaling pathway was activated in DAZAP1-OE MM cells. The analyses of RIP-seq and RIP-qPCR revealed that DAZAP1 activated alternative splicing of KIT proto-oncogene ligand (KITLG) mRNA. Further study validated that DAZAP1 increased ERK phosphorylation via modulating alternative splicing of KITLG mRNA to promote MM cell proliferation. In conclusion, we establish DAZAP1 as a tumor-promoting gene with therapeutic potential and provide mechanistic insights into targeting DAZAP1 as a new strategy for the diagnosis and treatment of MM.


APEX: Assessment of Proteasome Inhibition for Extending Remission; DAZAP1: Deleted in Azoospermia-Associated Protein 1; GEO: Gene expression omnibus; GEP: Gene expression profiling; KEGG: Kyoto encyclopedia of genes and genomes; KITLG: KIT proto-oncogene ligand; MGUS: Monoclonal gammopathy of undetermined significance; MM: Multiple myeloma; OS: Overall survival; RIP-seq: RNA Immunoprecipitation sequencing; TT2: Total therapy 2.