Matrin-3 promotes hepatocellular carcinoma progression by regulating cell cycle

Purpose: The overexpression of Matrin-3 (MATR3) is associated with tumor progression in several human tumors. However, the role of MATR3 in hepatocellular carcinoma (HCC) still remains unclear. In this study, we investigated the expression of MATR3 in HCC and elucidated the potential functions of MATR3 in HCC cells. Methods: The differential expression of MATR3 and its association with HCC were analyzed using the UALCAN database, Human Protein Atlas (HPA) database, GSE datasets and gene expression profiling interaction analysis2 (GEPIA2) database. Furthermore, we performed the CCK-8 assays, colony formation assays and flow cytometry analysis in HCC cell lines after knocking down MATR3. The MATR3-interacting proteins were identified by co‐immunoprecipitation and mass spectrometry (Co-IP/MS). Results: Overexpression of MATR3 protein and mRNA were observed in HCC. High MATR3 expression showed a prominent diagnostic value in HCC patients and significant correlations with clinical stages, tumor grades, nodal metastasis, TP53 mutant, poorer overall survival (OS) and disease-free survival (DFS). Moreover, downregulation of MATR3 inhibited proliferation and arrested cell cycle of HCC cells. Enrichment analysis results of MATR3-interacting proteins demonstrated that MATR3 might regulate cell cycle by interacting with DNA primase large subunit (PRIM2), chromobox protein homolog 5 (CBX5), and protein SEC13 homolog (SEC13). Conclusion: MATR3 could be a diagnostic and prognostic marker in HCC patients. Furthermore, MATR3 enhanced tumor progression by regulating the cell cycle of HCC and could be a promising candidate for targeted therapy.