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长链非编码 RNA 02298 通过靶向 miR-28-5p/CCDC6 通路促进 HCC 的恶性转化。

Long Non-coding RNA 02298 Promotes the Malignancy of HCC by Targeting the miR-28-5p/CCDC6 Pathway.

机构信息

Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, 210019, Jiangsu, China.

Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.

出版信息

Biochem Genet. 2024 Dec;62(6):4967-4986. doi: 10.1007/s10528-023-10662-9. Epub 2024 Feb 21.

Abstract

Hepatocellular carcinoma (HCC) is a malignancy characterized by a high fatality rate. Increasing evidence indicating that long non-coding RNAs (lncRNAs) play a regulatory role in hepatocellular carcinoma (HCC). Among them, the correlation between LINC02298 and HCC remains unknown. The expression and subcellular localization of LINC02298 in HCC tissues and cell lines were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Furthermore, the correlation between the expression of LINC02298 and clinicopathological features of HCC patients was analyzed. The regulatory effects of LINC02298 in HCC were investigated using colony formation, cell count Kit-8(CCK8), Transwell, EDU, cell cycle and apoptosis analysis. In addition, the expression of EMT-related proteins were detected by western blotting. Dual-luciferase reporter, RT-qPCR and rescue assays were employed to validate the involvement of the LINC02298/miR-28-5p/CCDC6 axis in the progression of HCC. The up-regulation of LINC02298 was observed in hepatocellular carcinoma (HCC) tissues and cells, and it was found to be correlated with a negative prognosis in patients with HCC. Overexpression of LINC02298 enhanced the proliferation, migration, invasion, and induction of Epithelial-Mesenchymal Transition (EMT) while suppressing apoptosis in HCC cells. LINC02298 bind to miR-28-5p to regulate the expression of CCDC6. Inhibition of miR-28-5p saved the inhibitory effect of shLINC02298, and knockdown of CCDC6 also saved the inhibitory effect of miR-28-5p on HCC in vitro and in vivo. LINC02298 regulates the expression of CCDC6 by sponging of miR-28-5p, thereby facilitating the the malignancy and EMT of HCC.

摘要

肝细胞癌 (HCC) 是一种具有高死亡率的恶性肿瘤。越来越多的证据表明,长非编码 RNA (lncRNA) 在肝细胞癌 (HCC) 中发挥调节作用。其中,LINC02298 与 HCC 之间的相关性尚不清楚。本研究通过实时定量聚合酶链反应 (RT-qPCR) 检测 HCC 组织和细胞系中 LINC02298 的表达和亚细胞定位。此外,分析了 LINC02298 的表达与 HCC 患者临床病理特征之间的相关性。通过集落形成、细胞计数试剂盒-8 (CCK8)、Transwell、EDU、细胞周期和凋亡分析研究了 LINC02298 在 HCC 中的调节作用。此外,通过 Western blot 检测 EMT 相关蛋白的表达。双荧光素酶报告、RT-qPCR 和挽救实验用于验证 LINC02298/miR-28-5p/CCDC6 轴在 HCC 进展中的作用。在肝癌组织和细胞中观察到 LINC02298 的上调,并且发现其与 HCC 患者的不良预后相关。LINC02298 的过表达增强了 HCC 细胞的增殖、迁移、侵袭和上皮-间充质转化 (EMT) 的诱导,同时抑制了细胞凋亡。LINC02298 与 miR-28-5p 结合,调节 CCDC6 的表达。抑制 miR-28-5p 挽救了 shLINC02298 的抑制作用,而 CCDC6 的敲低也挽救了 miR-28-5p 对 HCC 的体外和体内抑制作用。LINC02298 通过海绵吸附 miR-28-5p 调节 CCDC6 的表达,从而促进 HCC 的恶性转化和 EMT。

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