Li Mei, Cheng Yuan, Qiu Fakai, Mu Xudong, Zhai Pengtao, Li Zhubin, Liu Qunyi, Li Qianjin
Department of Minimally Invasive, Shaanxi Cancer Hospital, Xi'an, 710061, Shaanxi, China.
Department of Interventional Vascular, Yulin First Hospital, Yuxi Avenue, High tech Zone, Yuyang District, Yulin, 719054, Shaanxi, China.
Discov Oncol. 2025 Jun 18;16(1):1145. doi: 10.1007/s12672-025-02902-8.
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).
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.
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.
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.
本研究聚焦于长链非编码RNA内源性博尔纳病毒样核蛋白3假基因（EBLN3P）和微小RNA-323a-3p（miR-323a-3p）通过EPH受体A1（EphA1）对肝癌（HCC）细胞活性的影响。
评估EBLN3P、miR-323a-3p和EphA1在肝癌组织和细胞中的表达水平。随后，进一步分析EBLN3P表达与肝癌临床病理特征之间的联系。通过多种分子实验验证EBLN3P与miR-323a-3p以及miR-323a-3p与EphA1的结合位点。分别通过CCK-8实验、Transwell实验和流式细胞术评估肝癌细胞活性。建立体内皮下肿瘤抑制模型以验证肿瘤生长情况。
在EBLN3P沉默的肝癌细胞中，细胞增殖、侵袭和迁移能力显著下降，同时凋亡率升高。EBLN3P可竞争性结合miR-323a-3p以下调miR-323a-3p。miR-323a-3p过表达可抵消EBLN3P对肝癌细胞活性的致癌作用。miR-323a-3p直接靶向EphA1。EphA1过表达可抵消miR-323a-3p对肝癌细胞活性的抑制作用。体内实验表明，EBLN3P下调通过miR-323a-3p/EphA1轴抑制肿瘤生长。
EBLN3P通过调节miR-323a-3p/EphA1轴促进肝癌发展。干扰EBLN3P可通过上调miR-323a-3p和下调EphA1有效抑制肝癌细胞的增殖、迁移和侵袭。该机制为肝癌发病机制提供了新的分子证据，提示EBLN3P作为肝癌治疗的潜在靶点。未来研究应探索该轴与其他肿瘤相关信号通路之间的相互作用，以支持靶向治疗策略的开发。
