ZMYM4 Acts as a Potential Prognostic Biomarker and Promotes the Malignant Progression of Hepatocellular Carcinoma Cells: It Is Regulated by miR‐34a‐5p

Hepatocellular carcinoma (HCC) constitutes approximately 90% of all liver cancer cases. Targeted drugs demonstrate significant potential in the treatment of advanced HCC; however, it is imperative to investigate novel and promising therapeutic targets to overcome the limitations of current targeted therapies. Zinc-finger MYM-type containing 4 (ZMYM4) has frequently been identified as a fusion gene, but the biological function of ZMYM4 in HCC is still unclear. In this study, we utilized The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to investigate the expression levels of ZMYM4 in HCC and to evaluate the correlation between ZMYM4 expression levels and both clinical characteristics and survival outcomes of HCC patients. Subsequently, clinical samples were utilized for further validation. Subsequently, the impact of ZMYM4 knockdown on the malignant progression of HCC cells was examined through a series of in vitro experiments. The specific regulatory relationship between miR-34a-5p and ZMYM4 was confirmed through a luciferase reporter assay. Ultimately, the regulatory effect of miR-34a-5p on ZMYM4 expression in HCC cells was examined. Bioinformatics analysis and clinical sample detection revealed that ZMYM4 expression was significantly upregulated in HCC and correlated with clinical stages and unfavorable prognosis in patients. When ZMYM4 expression was knocked down, the proliferation, migration, and invasion capabilities of HCC cells were significantly inhibited, while the apoptosis rate was markedly increased. Overexpression of ZMYM4 produced opposing effects. In HCC cells, miR-34a-5p directly targets ZMYM4. Upon overexpression of miR-34a-5p, the malignant phenotype of HCC cells was significantly inhibited. Notably, the overexpression of miR-34a-5p partially mitigated the promotional effect of ZMYM4 upregulation on the malignant progression of HCC cells. In conclusion, ZMYM4 is specifically targeted by miR-34a-5p in HCC and promotes the malignant progression of HCC. This suggests that ZMYM4 may serve as a potential biomarker for both the treatment and prognosis of HCC.