Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the primary liver tumors with high incidence and mortality. RNA G-quadruplexes (rG4) are nucleic acid structures involved in gene expression and genome duplication. rG4 exerts its function by interacting with rG4-binding proteins. The carboxypyridostatin (cPDS), a specific ligand of rG4, are widely studied in numerous tumors. However, the role of cPDS in HCC and its regulatory mechanisms are not yet fully understood. Our study aimed to discuss the regulatory mode of cPDS on Baculoviral IAP Repeat Containing 3 (BIRC3) expression and its impact on proliferation, apoptosis, and other biologic functions in HCC. METHODS: We conducted colony formation, CCK8, Edu incorporation, scratch healing, and cell spheroid formation assays to analyze the function of cPDS on cell proliferation and migration. Additionally, we explored the role of cPDS in regulating BIRC3 expression by Western blot and qRT-PCR. Furthermore, we evaluated the impact of BIRC3 on cell proliferation and subcutaneous tumor formation in nude mice. Finally, we analyzed the regulatory mechanisms of cPDS on cell apoptosis by Western blot, qRT-PCR, flow cytometry, and Annexin V-FITC staining. RESULTS: Our results demonstrated that cPDS inhibited HCC cells proliferation and migration. Moreover, cPDS elevated the mRNA level while inhibiting the protein expression of BIRC3 in HCC cells. Overexpression of BIRC3 significantly enhanced the proliferation of HCC cells. In the nude mice model, BIRC3 significantly increased the tumor volume and weight. Mechanistically, cPDS promoted cell apoptosis via inhibiting BIRC3-mediated anti-apoptotic effect. CONCLUSION: Our findings revealed a critical role of rG4 ligand cPDS in HCC progression and indicate that cPDS may be used for HCC treatment considering its tumor inhibitory properties by regulating cell apoptosis.