Huang Shaobo, Zhang Jinling, He Ting, Zhou Jianping, Liu Zhigang
Cancer Center, the Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, China.
Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, the Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, China.
J Cell Mol Med. 2025 Mar;29(6):e70472. doi: 10.1111/jcmm.70472.
Midnolin (MIDN) is a protein coding gene that promotes the destruction of transcription factors encoded by immediate-early genes. Previous research has found that those immediate-early genes are involved in tumour progression. However, the role of MIDN is still not clearly identified in human cancers. With the help of the TCGA, GTEx, and HPA databases, we revealed that the expression of MIDN was disordered in cancers. MIDN is a potential prognostic biomarker in liver cancer and bladder cancer. Prognostic analysis indicates that the expression level of MIDN gains survival benefits or promotes progression in multiple tumours. After analysing the sequencing results of TCGA via Gene Set Enrichment Analysis (GSEA), results suggested the regulative role of MIDN in cell proliferation and tumour immunity. Single cell sequencing results revealed that MIDN is highly expressed in several tumour tissues and also expressed in immune cells. With the help of the ESTIMATE, TIMER, and CIBERSORT databases, we analysed the immune score, immune cell infiltration, and anti-cancer immunity cycle depending on the expression of MIDN. Results showed that low MIDN levels are tightly associated with high CD4 + T and NK cell infiltration. Furthermore, mutations of MIDN in cancers were significantly associated with immune cell infiltration. This study presents a robust link between the expression of MIDN and tumour progression across multiple cancer types. The MIDN/CTNNB1/MMP9 axis promotes liver cancer progression via inducing a suppressive tumour immune microenvironment.
Midnolin(MIDN)是一个蛋白质编码基因,它能促进即刻早期基因所编码的转录因子的降解。先前的研究发现,那些即刻早期基因参与肿瘤进展。然而,MIDN在人类癌症中的作用仍未明确。借助TCGA、GTEx和HPA数据库,我们发现MIDN在癌症中的表达紊乱。MIDN是肝癌和膀胱癌中一种潜在的预后生物标志物。预后分析表明,MIDN的表达水平在多种肿瘤中对生存有益或促进进展。通过基因集富集分析(GSEA)分析TCGA的测序结果后,结果提示MIDN在细胞增殖和肿瘤免疫中具有调节作用。单细胞测序结果显示,MIDN在几种肿瘤组织中高表达,在免疫细胞中也有表达。借助ESTIMATE、TIMER和CIBERSORT数据库,我们根据MIDN的表达分析了免疫评分、免疫细胞浸润和抗癌免疫周期。结果显示,低水平的MIDN与高CD4 + T细胞和NK细胞浸润密切相关。此外,癌症中MIDN的突变与免疫细胞浸润显著相关。本研究揭示了MIDN的表达与多种癌症类型的肿瘤进展之间的紧密联系。MIDN/CTNNB1/MMP9轴通过诱导抑制性肿瘤免疫微环境促进肝癌进展。