Abstract
Objective: This study focused on the capabilities of lncRNA endogenous bornavirus-like nucleoprotein 3, pseudogene (EBLN3P) and microRNA-323a-3p (miR-323a-3p) on hepatocellular carcinoma (HCC) cells activities via EPH receptor A1 (EphA1). Methods: Expression levels of EBLN3P, miR-323a-3p, and EphA1 were evaluated in HCC tissues and cells. Subsequently, we further analyzed the link between EBLN3P expression and HCC clinicopathological features. The binding sites of EBLN3P and miR-323a-3p, as well as miR-323a-3p and EphA1, were verified via various molecular assays. HCC cell activities were assessed by CCK-8 assay, Transwell assay and flow cytometry, respectively. An in vivo subcutaneous tumor inhibition model was performed to validate tumor growth. Results: In EBLN3P-silenced HCC cells, there was a notable decrease in cell proliferation, invasive, and migratory capabilities, accompanied by an enhanced apoptosis rate. EBLN3P could competitively bind miR-323a-3p to downregulate miR-323a-3p. Overexpression of miR-323a-3p neutralized the oncogenic role of EBLN3P on HCC cell activities. miR-323a-3p directly targeted EphA1. Overexpression of EphA1 counteracted the suppressive role of miR-323a-3p on HCC cell activities. In vivo experiments demonstrated that downregulation of EBLN3P inhibited tumor growththrough the miR-323a-3p/EphA1 axis. Conclusion: EBLN3P promotes HCC development by regulating the miR-323a-3p/EphA1 axis. Interfering with EBLN3P effectively restrains proliferation, migration, and invasion of HCC cells by upregulating miR-323a-3p and downregulating EphA1. This mechanism provides new molecular evidence for HCC pathogenesis, suggesting EBLN3P as a potential target in HCC treatment. Future research should explore the interaction between this axis and other tumor-related signaling pathways to support the development of targeted therapeutic strategies.