3'UTR shortening of ZCRB1 promotes malignant progression of hepatocellular carcinoma through GOLM1.

Hepatocellular carcinoma (HCC) is the main type of human liver cancer, with high recurrence and mortality rates. We herein report that an elevated proportion of ZCRB1 mRNA isoforms harboring short 3'UTRs was observed in HCC tissues, leading to upregulated ZCRB1 protein expression. ZCRB1 knockdown via shRNAs markedly suppressed cell proliferation, colony formation, migration and invasion in vitro, and impeded tumor growth and lung metastasis in xenograft models. In terms of the downstream regulatory mechanism, ZCRB1 was verified to positively modulate GOLM1 through direct post‑transcriptional binding to the GOLM1 3'UTR. Rescue assays confirmed that the impaired cell proliferation, colony formation, migration, invasion as well as in vivo tumor growth and metastasis induced by ZCRB1 knockdown could be rescued via exogenous GOLM1 overexpression. Furthermore, high ZCRB1 expression was correlated with lymph node metastasis, advanced TNM stage, poorer overall survival (OS) and disease‑free survival (DFS) in patients with HCC. Collectively, our findings offer novel mechanistic insights into the oncogenic function of ZCRB1 in HCC, indicating that ZCRB1 may serve as a promising therapeutic target for HCC treatment.