RBP7 knockdown inhibits proliferation of human hepatocellular carcinoma and activates the p38 MAPK pathway

Jinhai Li^1,2*HUawei Zhai²Fujing Cai²Xian Zhang³Yu Zhou²Maolin Yan^1,4Huachun Sun¹Haifeng Zhang¹Guangzheng Sun²Minghui Zhu²Jing Yuan⁵Ningxin Zhang³Maolin Yan¹

• ¹Shengli Clinical Medical College, Fujian Medical University, Fuzhou, China
• ²Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China
• ³Wenzhou Medical University, Wenzhou, Zhejiang Province, China
• ⁴Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Zhuang Region, China
• ⁵Zhenjiang Hospital of Integrated Traditional Chinese and Western Medicine, Zhenjiang, Jiangsu Province, China

Background: Retinoid metabolism is critical for maintaining liver homeostasis, and its dysregulation is closely associated with liver diseases. Retinol binding protein 7 (RBP7) involves in retinoids transport, particularly in liver, indicating its importance in hepatic functions. However, its specific role in hepatocellular carcinoma (HCC) tumorigenesis remains unclear and needs to further investigation.Methods: Bioinformatics was employed to assess RBP7 expression across different cohorts.The expression level of RBP7 in cells were further validated using qRT-PCR and western blot. Additionally, we investigated the impact of RBP7 knockdown on cell cycle-related genes, apoptosis-related proteins, and p38 MAPK signaling activity. Functional assays, including CCK8, colony formation, flow cytometry (FACS) analysis, Annexin V/7-AAD staining and xenograft tumor assay, were performed to determine the vitro and in vivo role of RBP7. Survival analysis was conducted to evaluate the correlation between RBP7 expression and the prognosis of HCC patients.Results: RBP7 is frequently elevated in HCC tumor tissues, particularly in early-stage patients. Notably, high RBP7 expression is closely correlated with overall survival (OS) and disease-specific survival (DSS) in HCC patients. Knockdown of RBP7 inhibited cell proliferation in vitro and suppressed tumor growth in vivo by inducing cell cycle arrest and apoptosis. Mechanistically, we found that RBP7 knockdown-induced suppression of HCC cell proliferation was associated with increased phosphorylation of p38 MAPK.4 Conclusion: Our findings demonstrate that RBP7 suppression activates p38 MAPK signaling pathway, leading to impaired cell proliferation. These results suggest that RBP7 may serve as both a prognostic biomarker and a promising therapeutic target for HCC.