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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.
Abbreviations
| MATR3 | = | matrin-3; |
| HCC | = | hepatocellular carcinoma; |
| ICIs | = | immune checkpoint inhibitors; |
| NMPs | = | nuclear matrix proteins; |
| Co-IP/MS | = | co‐immunoprecipitationandmassspectrometry; |
| TCGA-LIHC | = | Liver Hepatocellular Carcinoma Project of The Cancer Genome Atlas; |
| ICGC-LIRI-JP | = | Liver Cancer-RIKEN, Japan Project from International Cancer Genome Consortium; |
| GEO | = | Gene Expression Omnibus; |
| ROC | = | receiver operating characteristic; |
| KM | = | Kaplan-Meier; |
| PPI | = | protein-protein interaction; |
| AUC | = | area under curve; |
| PBS | = | phosphate buffered saline; |
| CCK-8 | = | Cell Counting Kit-8; |
| CDK6 | = | cyclin-dependent kinase 6; |
| CCND1 | = | cyclin D1; |
| CCND2 | = | cyclin D2; |
| p21 | = | cyclin-dependent kinase inhibitor p21; |
| p27 | = | cyclin-dependent kinase inhibitor p27; |
| CDK4 | = | cyclin-dependent kinase 4; |
| CCNE1 | = | cyclin E1; |
| TIICs | = | tumor-infiltrating immune cells; |
| TAM | = | tumor-associated macrophage; |
| RFC2 | = | replication factor C 2; |
| PRIM2 | = | DNA primase subunit 2 |
Disclosure statement
No potential conflict of interest was reported by the author(s).
Consent to publish
All authors agreed to publish the article.
Credit Author Statement
Hengjing He and Muhammad Jamal: Investigation, Methodology, Validation, Formal analysis, Writing – original draft. Xingruo Zeng: Investigation, Resources. Yufei Lei: Investigation, Resources. Di Xiao: Investigation, Resources. Zimeng Wei: Investigation, Resources. Chengjie Zhang: Investigation, Resources. Xiaoyu Zhang: Investigation, Resources. Shan Pan: Investigation, Resources, Data curation. Qianshan Ding: Investigation, Resources, Data curation. Haiyan Tan: Conceptualization, Formal analysis, Resources. Songping Xie: Conceptualization, Formal analysis, Resources. Qiuping Zhang: Conceptualization, Investigation, Data curation, Funding acquisition, Project administration, Supervision, Writing – review & editing.
Data availability statement
All datasets used and analyzed during this study are available from the corresponding author on reasonable request.
Ethics approval
This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Renmin Hospital of Wuhan University.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/15384101.2024.2305535