Department of Hepatobiliary Surgery, The People's Hospital of Rongchang District, Chongqing, China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Int J Med Sci. 2023 Jan 1;20(1):23-34. doi: 10.7150/ijms.68778. eCollection 2023.
This study aimed to explore the role of lncRNA RPPH1 in hepatocellular carcinoma. The expression of RPPH1 and miR-122 was determined by Real-time PCR. Cell proliferation and colony formation assays were employed to monitor cell growth . Wound healing and Transwell assays were applied to detect cell migration and invasion. A dual-luciferase reporter assay was used to verify the interaction between RPPH1 and miR-122. The function of RPPH1 was illustrated by xenograft tumor models. The results showed that the expression of RPPH1 was markedly upregulated in human HCC specimens and cell lines compared to normal controls. However, the trend of miR-122 was the opposite. RPPH1 facilitates the proliferation, migration, and invasion of HCC cells and synchronously suppresses cell apoptosis. The dual-luciferase assay confirmed the relationship between RPPH1 and miR-122. Rescue experiments showed that RPPH1 acted as a competing endogenous RNA (ceRNA) by sponging miR-122 in HCC cells. Moreover, RPPH1 positively regulated the expression of Wnt1 and its downstream targets through miR-122. Our study demonstrates for the first time that RPPH1 promotes HCC progression via the miR-122/Wnt1/β-catenin axis, which may represent a valuable therapeutic target for patients with HCC.
本研究旨在探索 lncRNA RPPH1 在肝细胞癌中的作用。通过实时 PCR 测定 RPPH1 和 miR-122 的表达。采用细胞增殖和集落形成实验监测细胞生长。划痕愈合和 Transwell 实验用于检测细胞迁移和侵袭。双荧光素酶报告基因实验用于验证 RPPH1 和 miR-122 之间的相互作用。通过异种移植肿瘤模型阐明了 RPPH1 的功能。结果表明,与正常对照相比,人 HCC 标本和细胞系中 RPPH1 的表达明显上调。然而,miR-122 的趋势相反。RPPH1 促进 HCC 细胞的增殖、迁移和侵袭,同时抑制细胞凋亡。双荧光素酶实验证实了 RPPH1 和 miR-122 之间的关系。挽救实验表明,RPPH1 在 HCC 细胞中作为竞争性内源 RNA (ceRNA) 通过海绵吸附 miR-122 发挥作用。此外,RPPH1 通过 miR-122 正向调节 Wnt1 及其下游靶基因的表达。本研究首次证明,RPPH1 通过 miR-122/Wnt1/β-catenin 轴促进 HCC 进展,这可能代表 HCC 患者有价值的治疗靶点。