Open Access

RNA‑binding protein MBNL1 regulates tumor growth, chemosensitivity and antitumor immunity in lung adenocarcinoma by controlling the expression of tumor suppressor RNF125

  • Authors:
    • Yubo Yan
    • Xianglong Kong
    • Xiangyuan Jin
    • Jianlong Bu
    • Boxiong Ni
    • Zuqin Rao
    • Junnan Guo
    • Shidong Xu
  • View Affiliations

  • Published online on: May 2, 2025     https://doi.org/10.3892/or.2025.8907
  • Article Number: 74
  • Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ring finger protein 125 (RNF125), a ubiquitin E3 ligase, has been reported to act as a tumor suppressor in several cancers, but its precise function in lung adenocarcinoma (LUAD) has not been elucidated. In the present study, through bioinformatics analysis and immunohistochemistry in LUAD and non‑cancerous samples, it was demonstrated that RNF125 was significantly downregulated in lung cancer. Low levels of RNF125 expression were associated with metastatic status, advanced tumor stage and poor overall survival in LUAD. The results of gain‑ and loss‑of‑function experiments demonstrated that RNF125 inhibited proliferation, colony formation, migration and invasion of LUAD cells. In addition, RNF125 increased the sensitivity of LUAD cells to cisplatin. Mechanistically, RNF125 interacted with programmed cell death ligand 1 (PD‑L1) and reduced PD‑L1 expression levels in LUAD cells. Furthermore, IL‑2 secretion by Jurkat T cells was significantly suppressed when co‑cultured with RNF125‑silenced LUAD cells. NK‑92 cell lysis of RNF125‑silenced LUAD cells was also weaker compared with that of control LUAD cells, suggesting that RNF125 knockdown enhanced the immune evasion ability of LUAD cells. Notably, the results of the present study identified that the RNA‑binding protein muscleblind‑like 1 (MBNL1) is the upstream regulator of RNF125 in LUAD. MBNL1 increased the stability of the RNF125 transcript in LUAD cells and knockdown of RNF125 reversed the antitumor effect of MBNL1 on LUAD cells. In conclusion, the present study demonstrated the tumor suppressor role of RNF125 in LUAD and implicated MBNL1 as an upstream regulator of RNF125 in LUAD. These findings contributed to an improved understanding of the molecular features of LUAD progression.
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July-2025
Volume 54 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Yan Y, Kong X, Jin X, Bu J, Ni B, Rao Z, Guo J and Xu S: RNA‑binding protein MBNL1 regulates tumor growth, chemosensitivity and antitumor immunity in lung adenocarcinoma by controlling the expression of tumor suppressor RNF125. Oncol Rep 54: 74, 2025.
APA
Yan, Y., Kong, X., Jin, X., Bu, J., Ni, B., Rao, Z. ... Xu, S. (2025). RNA‑binding protein MBNL1 regulates tumor growth, chemosensitivity and antitumor immunity in lung adenocarcinoma by controlling the expression of tumor suppressor RNF125. Oncology Reports, 54, 74. https://doi.org/10.3892/or.2025.8907
MLA
Yan, Y., Kong, X., Jin, X., Bu, J., Ni, B., Rao, Z., Guo, J., Xu, S."RNA‑binding protein MBNL1 regulates tumor growth, chemosensitivity and antitumor immunity in lung adenocarcinoma by controlling the expression of tumor suppressor RNF125". Oncology Reports 54.1 (2025): 74.
Chicago
Yan, Y., Kong, X., Jin, X., Bu, J., Ni, B., Rao, Z., Guo, J., Xu, S."RNA‑binding protein MBNL1 regulates tumor growth, chemosensitivity and antitumor immunity in lung adenocarcinoma by controlling the expression of tumor suppressor RNF125". Oncology Reports 54, no. 1 (2025): 74. https://doi.org/10.3892/or.2025.8907