2. Academic Validation
  3. USP10-stabilized IGF2BP3 promotes tumor growth via m6A-modified SKP2 mRNA in non-small-cell lung cancer

USP10-stabilized IGF2BP3 promotes tumor growth via m6A-modified SKP2 mRNA in non-small-cell lung cancer

  • Int J Biol Macromol. 2025 Sep 17;329(Pt 1):147753. doi: 10.1016/j.ijbiomac.2025.147753.
Cong Wang 1,  Xuyang Hou 1,  Qing Guan 1,  Huiling Zhou 1,  Yong Luo 1,  Wancun Jin 2,  Fan Bai 2,  Lijun Liu 1,  Jian Wang 1,  Li Xie 2,  Feng Li 2,  Haidan Liu 3
Affiliations

Affiliations

  • 1 Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China; Clinical Center for Gene Diagnosis and Therapy, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
  • 2 Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
  • 3 Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China; Clinical Center for Gene Diagnosis and Therapy, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. Electronic address: haidanliu@csu.edu.cn.
PMID: 40972933 DOI: 10.1016/j.ijbiomac.2025.147753
Abstract

Non-small-cell lung Cancer (NSCLC) is a common and deadly Cancer. IGF2BP3 has been determined as an oncogenic N6-methyladenosine modification "reader" in solid tumors. However, the role and mechanism of IGF2BP3 in NSCLC remains largely unknown. Here, we demonstrated that aberrant IGF2BP3 expression is associated with poor prognosis in NSCLC. IGF2BP3 deficiency significantly restrains cell proliferation and tumor growth in vitro and in vivo. Mechanistically, IGF2BP3 positively regulates S-Phase Kinase Associated Protein 2 (SKP2) expression. IGF2BP3 binds and stabilizes SKP2 mRNA in an m6A-dependent manner, with an elevated SKP2 expression. Further, we proved that USP10 acts as a novel Deubiquitinase (DUB) of IGF2BP3 by screening a panel of 58 DUBs. USP10 increases IGF2BP3 expression by removing K48-linked polyubiquitination chains from IGF2BP3 and inhibiting its proteasome-mediated degradation.

Keywords

Deubiquitination; IGF2BP3; N6-methyladenosine; NSCLC; SKP2; Tumor growth.

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