m6A reader IGF2BP2-stabilized lncRNA LHX1-DT inhibits renal cell carcinoma (RCC) cell proliferation and invasion by sponging miR-590-5p
N6-methyladenosine (m6A) has been established as a critical regulator in various human cancers. However, the role of m6A modification in renal cell carcinoma (RCC) and its interaction with long non-coding RNA LHX1-DT (LHX1-DT) remains unclear. Differentially expressed lncRNAs and m6A levels were identified through microarray analysis. The interaction between IGF2BP2 and LHX1-DT was examined via RNA immunoprecipitation and luciferase reporter assays. LHX1-DT expression was found to be downregulated in RCC tissues, and reduced expression of LHX1-DT was associated with poor overall survival in RCC patients. Functional assays demonstrated that overexpression of LHX1-DT significantly inhibited RCC cell proliferation and invasion. The m6A reader protein IGF2BP2, mediated by METTL14, recognized the m6A modification site on LHX1-DT and promoted its stability. Additionally, LHX1-DT acted as a competing endogenous RNA (ceRNA) by sponging miR-590-5p, which in turn downregulated PDCD4, thereby inhibiting RCC cell proliferation and invasion. LHX1-DT serves as an independent prognostic biomarker for RCC, and the IGF2BP2/LHX1-DT/miR-590-5p/PDCD4 axis represents a novel therapeutic target for RCC progression.
Authors
- Xiangyun You
- Xiaonan Chen (ORCID: https://orcid.org/0000-0003-3714-6815)
- Chunming Zhu
- Kefeng Wang (ORCID: https://orcid.org/0000-0003-0014-9182)
- Jie Xu
- Dan Dong
- Jiahe Wang (ORCID: https://orcid.org/0009-0008-6321-140X)
- Ruiming Li (ORCID: https://orcid.org/0000-0002-2207-2553)
Institutions
- China Three Gorges University (CN)
- Yichang Central People's Hospital (CN)
- China Medical University (CN)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2025-06-17
- DOI
- https://doi.org/10.1038/s41698-025-00958-x
- Citations
- 2
- Primary Topic
- Cancer-related molecular mechanisms research
- Type
- article
- Field-Weighted Citation Impact
- 1.87
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Liaoning Province
- China Medical University
- Department of Science and Technology of Liaoning Province
- Shengjing Hospital