ZCRB1 promotes proliferation and metastasis of lung squamous cell carcinoma by stabilizing DSG3 mRNA.

Lung squamous cell carcinoma (LUSC) is a major subtype of non-small cell lung cancer (NSCLC) with limited therapeutic targets and poor prognosis. Zinc finger CCHC-type RNA-binding protein 1 (ZCRB1) has been implicated in RNA metabolism, yet its role in LUSC remains largely unexplored. In this study, we found that ZCRB1 was significantly overexpressed in NSCLC tissues, particularly in LUSC, and high ZCRB1 expression was associated with poorer overall and disease-free survival. ZCRB1 knockdown markedly suppressed LUSC cell proliferation, migration, and invasion in vitro and inhibited tumor growth and pulmonary metastasis in vivo. Bioinformatic and experimental analyses identified DSG3 as a key downstream target positively correlated with ZCRB1 expression in LUSC tissues. Mechanistically, ZCRB1 directly bound to DSG3 mRNA and enhanced its stability. Importantly, DSG3 overexpression partially reversed the inhibitory effects of ZCRB1 knockdown on LUSC cell malignant phenotypes both in vitro and in vivo. In conclusion, ZCRB1 functions as an oncogenic RNA-binding protein in LUSC by promoting tumor growth and metastasis through stabilization of DSG3 mRNA. Targeting the ZCRB1-DSG3 axis may represent a novel therapeutic strategy for lung squamous cell carcinoma.