m6A reader IGF2BP2-stabilized lncRNA LHX1-DT inhibits renal cell carcinoma (RCC) cell proliferation and invasion by sponging miR-590-5p
Abstract 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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-06-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-025-00958-x |
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| author | Chunming Zhu Ruiming Li Xiangyun You Jie Xu Jiahe Wang Dan Dong Xiaonan Chen Kefeng Wang |
| author_facet | Chunming Zhu Ruiming Li Xiangyun You Jie Xu Jiahe Wang Dan Dong Xiaonan Chen Kefeng Wang |
| author_sort | Chunming Zhu |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-2be80b517f0543f5b2f7d5e45fab47e4 |
| institution | Kabale University |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-2be80b517f0543f5b2f7d5e45fab47e42025-08-20T03:47:24ZengNature Portfolionpj Precision Oncology2397-768X2025-06-019111710.1038/s41698-025-00958-xm6A reader IGF2BP2-stabilized lncRNA LHX1-DT inhibits renal cell carcinoma (RCC) cell proliferation and invasion by sponging miR-590-5pChunming Zhu0Ruiming Li1Xiangyun You2Jie Xu3Jiahe Wang4Dan Dong5Xiaonan Chen6Kefeng Wang7Department of Family Medicine, Shengjing Hospital of China Medical UniversityDepartment of Urology, Shengjing Hospital of China Medical UniversityDepartment of Urology, Shengjing Hospital of China Medical UniversityDepartment of Urology, Shengjing Hospital of China Medical UniversityDepartment of Family Medicine, Shengjing Hospital of China Medical UniversityCollege of Basic Medical Science, China Medical UniversityDepartment of Urology, Shengjing Hospital of China Medical UniversityDepartment of Urology, Shengjing Hospital of China Medical UniversityAbstract 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.https://doi.org/10.1038/s41698-025-00958-x |
| spellingShingle | Chunming Zhu Ruiming Li Xiangyun You Jie Xu Jiahe Wang Dan Dong Xiaonan Chen Kefeng Wang m6A reader IGF2BP2-stabilized lncRNA LHX1-DT inhibits renal cell carcinoma (RCC) cell proliferation and invasion by sponging miR-590-5p npj Precision Oncology |
| title | m6A reader IGF2BP2-stabilized lncRNA LHX1-DT inhibits renal cell carcinoma (RCC) cell proliferation and invasion by sponging miR-590-5p |
| title_full | m6A reader IGF2BP2-stabilized lncRNA LHX1-DT inhibits renal cell carcinoma (RCC) cell proliferation and invasion by sponging miR-590-5p |
| title_fullStr | m6A reader IGF2BP2-stabilized lncRNA LHX1-DT inhibits renal cell carcinoma (RCC) cell proliferation and invasion by sponging miR-590-5p |
| title_full_unstemmed | m6A reader IGF2BP2-stabilized lncRNA LHX1-DT inhibits renal cell carcinoma (RCC) cell proliferation and invasion by sponging miR-590-5p |
| title_short | m6A reader IGF2BP2-stabilized lncRNA LHX1-DT inhibits renal cell carcinoma (RCC) cell proliferation and invasion by sponging miR-590-5p |
| title_sort | m6a reader igf2bp2 stabilized lncrna lhx1 dt inhibits renal cell carcinoma rcc cell proliferation and invasion by sponging mir 590 5p |
| url | https://doi.org/10.1038/s41698-025-00958-x |
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