Midnolin Correlates With Anti-Tumour Immunity and Promotes Liver Cancer Progression Through β-Catenin

Shaobo Huang, Jinling Zhang, Ting He, Jianping Zhou, Zhigang Liu
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Abstract

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.

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米诺林与抗肿瘤免疫相关,并通过β-连环蛋白促进肝癌进展。
Midnolin (MIDN)是一种促进立即早期基因编码的转录因子破坏的蛋白质编码基因。先前的研究发现,这些早期基因与肿瘤的发展有关。然而,MIDN在人类癌症中的作用仍未被明确确定。在TCGA、GTEx和HPA数据库的帮助下,我们发现MIDN在癌症中的表达是紊乱的。MIDN是肝癌和膀胱癌的潜在预后生物标志物。预后分析表明,在多种肿瘤中,表达水平的MIDN可获得生存益处或促进进展。通过基因集富集分析(Gene Set Enrichment Analysis, GSEA)对TCGA的测序结果进行分析,结果表明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,也在免疫细胞中表达。借助ESTIMATE、TIMER和CIBERSORT数据库,我们分析了MIDN表达对免疫评分、免疫细胞浸润和抗癌免疫周期的影响。结果表明,低MIDN水平与高CD4 + T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。这项研究表明,在多种癌症类型中,MIDN的表达与肿瘤进展之间存在着强有力的联系。MIDN/CTNNB1/MMP9轴通过诱导抑制性肿瘤免疫微环境促进肝癌进展。
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期刊介绍: The Journal of Cellular and Molecular Medicine serves as a bridge between physiology and cellular medicine, as well as molecular biology and molecular therapeutics. With a 20-year history, the journal adopts an interdisciplinary approach to showcase innovative discoveries. It publishes research aimed at advancing the collective understanding of the cellular and molecular mechanisms underlying diseases. The journal emphasizes translational studies that translate this knowledge into therapeutic strategies. Being fully open access, the journal is accessible to all readers.
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