Department of Geriatric Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 610041, China.
State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Oncol Res. 2022 Aug 1;29(3):175-187. doi: 10.32604/or.2022.03550. eCollection 2021.
Long intergenic non-protein coding RNA 1124 (LINC01124) has been identified as an important regulator of non-small-cell lung cancer. However, the expression and detailed role of LINC01124 in hepatocellular carcinoma (HCC) remain unestablished to date. Therefore, this study aimed to elucidate the role of LINC01124 in the aggressiveness of HCC cells and identify the underlying regulatory mechanism. Quantitative reverse transcriptase-polymerase chain reaction was performed to measure the expression of LINC01124 in HCC. Cell Counting Kit-8 assay, Transwell cell migration and invasion assays, and a xenograft tumor model were used to investigate the function of LINC01124 in HCC cells, and bioinformatics analysis, RNA immunoprecipitation, luciferase reporter assay, and rescue experiments were used to elucidate the underlying mechanisms. Herein, LINC01124 overexpression was confirmed in HCC tissues as well as cell lines. Further, the downregulation of LINC01124 decreased HCC cell proliferation, migration, and invasion , whereas the upregulation of LINC01124 triggered the opposite results. Additionally, LINC01124 ablation impaired tumor growth . Mechanistic analyses revealed that LINC01124 functions as a competing endogenous RNA to sponge microRNA-1247-5p (miR-1247-5p) in HCC cells. Moreover, forkhead box O3 (FOXO3) was identified as a direct target of miR-1247-5p. FOXO3 was positively regulated by LINC01124 in HCC cells through the sequestration of miR-1247-5p. Finally, rescue assays revealed that the inhibition of miR-1247-5p or overexpression of FOXO3 reversed the effects of LINC01124 silencing on the HCC cell malignant phenotype. In summary, LINC01124 plays a tumor-promoting role in HCC by regulating the miR-1247-5p-FOXO3 axis. The LINC01124-miR-1247-5p-FOXO3 pathway may provide a foundation for the identification of alternative therapies for HCC.
长链非编码 RNA 1124（LINC01124）已被确定为非小细胞肺癌的重要调控因子。然而，LINC01124在肝细胞癌（HCC）中的表达和详细作用至今尚未确定。因此，本研究旨在阐明 LINC01124在 HCC 细胞侵袭性中的作用，并确定其潜在的调控机制。采用实时定量逆转录聚合酶链反应检测 HCC 中 LINC01124 的表达。通过细胞计数试剂盒-8 检测、Transwell 细胞迁移和侵袭检测以及异种移植肿瘤模型来研究 LINC01124 在 HCC 细胞中的功能，同时进行生物信息学分析、RNA 免疫沉淀、荧光素酶报告基因检测和挽救实验来阐明其潜在机制。在此，LINC01124 在 HCC 组织和细胞系中过表达。进一步，下调 LINC01124 降低了 HCC 细胞的增殖、迁移和侵袭能力，而上调 LINC01124 则产生相反的结果。此外，LINC01124 缺失抑制了肿瘤生长。机制分析表明，LINC01124 在 HCC 细胞中作为竞争性内源性 RNA 来海绵 microRNA-1247-5p（miR-1247-5p）。此外，叉头框蛋白 O3（FOXO3）被鉴定为 miR-1247-5p 的直接靶标。LINC01124 通过海绵 miR-1247-5p 正向调节 HCC 细胞中的 FOXO3。最后，挽救实验表明，抑制 miR-1247-5p 或过表达 FOXO3 可逆转 LINC01124 沉默对 HCC 细胞恶性表型的影响。总之，LINC01124 通过调节 miR-1247-5p-FOXO3 轴在 HCC 中发挥促肿瘤作用。LINC01124-miR-1247-5p-FOXO3 通路可能为 HCC 替代治疗的鉴定提供基础。
