Zhu Chunming, Li Ruiming, You Xiangyun, Xu Jie, Wang Jiahe, Dong Dan, Chen Xiaonan, Wang Kefeng
Department of Family Medicine, Shengjing Hospital of China Medical University, Shenyang, China.
Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China.
NPJ Precis Oncol. 2025 Jun 17;9(1):193. doi: 10.1038/s41698-025-00958-x.
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.
N6-甲基腺嘌呤（m6A）已被确认为多种人类癌症中的关键调节因子。然而，m6A修饰在肾细胞癌（RCC）中的作用及其与长链非编码RNA LHX1-DT（LHX1-DT）的相互作用仍不清楚。通过微阵列分析鉴定了差异表达的长链非编码RNA和m6A水平。通过RNA免疫沉淀和荧光素酶报告基因检测来检测IGF2BP2与LHX1-DT之间的相互作用。研究发现，LHX1-DT在RCC组织中表达下调，LHX1-DT表达降低与RCC患者的总生存期较差相关。功能实验表明，LHX1-DT的过表达显著抑制RCC细胞的增殖和侵袭。由METTL14介导的m6A阅读蛋白IGF2BP2识别LHX1-DT上的m6A修饰位点并促进其稳定性。此外，LHX1-DT通过吸附miR-590-5p作为竞争性内源RNA（ceRNA），进而下调PDCD4，从而抑制RCC细胞的增殖和侵袭。LHX1-DT作为RCC的独立预后生物标志物，IGF2BP2/LHX1-DT/miR-590-5p/PDCD4轴代表RCC进展的新治疗靶点。
