PDF(Pubmed)
Abstract：
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The oncogenic role of Matrin-3 (MATR3), an a nuclear matrix protein, in HCC remains largely unknown. Here, we document the biological function of MATR3 in HCC based on integrated bioinformatics analysis and functional studies. According to the TCGA database, MATR3 expression was found to be positively correlated with clinicopathological characteristics in HCC. The receiver operating characteristic (ROC) curve and Kaplan-Meier (KM) curve displayed the diagnostic and prognostic potentials of MATR3 in HCC patients, respectively. Pathway enrichment analysis represented the enrichment of MATR3 in various molecular pathways, including the regulation of the cell cycle. Functional assays in HCC cell lines showed reduced proliferation of cells with stable silencing of MATR3. At the same time, the suppressive effects of MATR3 depletion on HCC development were verified by xenograft tumor experiments. Moreover, MATR3 repression also resulted in cell cycle arrest by modulating the expression of cell cycle-associated genes. In addition, the interaction of MATR3 with cell cycle-regulating factors in HCC cells was further corroborated with co-immunoprecipitation and mass spectrometry (Co-IP/MS). Furthermore, CIBERSORT and TIMER analyses showed an association between MATR3 and immune infiltration in HCC. In general, this study highlights the novel oncogenic function of MATR3 in HCC, which could comprehensively address how aberrant changes in the cell cycle promote HCC development. MATR3 might serve as a prognostic predictor and therapeutic target for HCC patients.
摘要：
肝细胞癌（HCC）是全球癌症相关死亡率的主要原因之一。Matrin-3（MATR3）的致癌作用，一种核基质蛋白，在HCC中仍然未知。这里,我们基于综合生物信息学分析和功能研究记录了MATR3在HCC中的生物学功能。根据TCGA数据库,发现MATR3的表达与HCC的临床病理特征呈正相关。受试者工作特征（ROC）曲线和Kaplan-Meier（KM）曲线显示了MATR3在HCC患者中的诊断和预后潜力。分别。途径富集分析代表了MATR3在各种分子途径中的富集，包括细胞周期的调节。HCC细胞系中的功能测定显示，随着MATR3的稳定沉默，细胞增殖减少。同时,通过异种移植肿瘤实验验证了MATR3耗竭对HCC发展的抑制作用.此外，MATR3抑制还通过调节细胞周期相关基因的表达而导致细胞周期停滞。此外,联合免疫沉淀和质谱(Co-IP/MS)进一步证实了MATR3与HCC细胞中细胞周期调节因子的相互作用.此外，CIBERSORT和TIMER分析显示MATR3与HCC中的免疫浸润之间存在关联。总的来说,这项研究强调了MATR3在HCC中的新致癌功能，这可以全面解决细胞周期的异常变化如何促进肝癌的发展。MATR3可能作为HCC患者的预后预测因子和治疗靶点。
