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长链非编码 RNA NEAT1 通过作为 miR-320a 的分子海绵并靶向 L 抗原家族成员 3 调节肝癌细胞的增殖和迁移。

lncRNA NEAT1 regulates the proliferation and migration of hepatocellular carcinoma cells by acting as a miR‑320a molecular sponge and targeting L antigen family member 3.

机构信息

Organ Transplant Center, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.

Organ Transplant Center, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.

出版信息

Int J Oncol. 2020 Oct;57(4):1001-1012. doi: 10.3892/ijo.2020.5108. Epub 2020 Aug 10.

Abstract

Long non‑coding RNAs (lncRNAs) serve a pivotal role in hepatocellular carcinoma (HCC) progression and have been confirmed to participate in the carcinogenesis and development of HCC. Certain studies have focused on lncRNA nuclear enriched abundant transcript 1 (NEAT1) in HCC. However, the relationship between lncRNA NEAT1 and HCC remains unclear. The present study found that NEAT1 was significantly overexpressed in HCC cell lines compared with LX‑2 hepatic stellate cells. NEAT1 expression in Huh7 and MHCC‑97H cells was increased following transfection with lentivirus (LV)‑NEAT1 but inhibited by LV‑short hairpin NEAT1. Knockdown of NEAT1 significantly repressed HCC cell viability, increased cell apoptosis, and inhibited cell migration and invasion capacity. By contrast, upregulation of NEAT1 demonstrated the reverse effects. Furthermore, microRNA‑320a (miR‑230a) was predicted to be a direct target of NEAT1 and was significantly reduced in HCC cells. Additionally, a luciferase activity reporter assay and RNA immunoprecipitation assay were performed to confirm the interaction between miR‑320a and NEAT1. Using a dual‑luciferase activity assay, L antigen family member 3 (LAGE3) was found to be a target of miR‑320a. Finally, in vivo nude mouse models were established, and the results indicated that NEAT1 suppressed HCC progression by targeting miR‑320a. In conclusion, the present findings revealed that the NEAT1/miR‑320a/LAGE3 axis participates in HCC development and that NEAT1 could be used as a biomarker for HCC.

摘要

长链非编码 RNA(lncRNA)在肝细胞癌(HCC)的进展中起着关键作用,并且已经证实其参与了 HCC 的癌变和发展。某些研究集中在 HCC 中的 lncRNA 核富集丰富转录本 1(NEAT1)上。然而,lncRNA NEAT1 与 HCC 之间的关系仍不清楚。本研究发现,与 LX-2 肝星状细胞相比,HCC 细胞系中 NEAT1 的表达显著上调。用慢病毒(LV)-NEAT1 转染 Huh7 和 MHCC-97H 细胞后,NEAT1 的表达增加,但用 LV-短发夹 NEAT1 抑制。敲低 NEAT1 可显著抑制 HCC 细胞活力,增加细胞凋亡,并抑制细胞迁移和侵袭能力。相比之下,上调 NEAT1 则表现出相反的效果。此外,miR-320a(miR-230a)被预测为 NEAT1 的直接靶标,并且在 HCC 细胞中显著减少。此外,还进行了荧光素酶活性报告基因检测和 RNA 免疫沉淀测定以证实 miR-320a 和 NEAT1 之间的相互作用。通过双荧光素酶活性测定发现,L 抗原家族成员 3(LAGE3)是 miR-320a 的靶标。最后,建立了体内裸鼠模型,结果表明 NEAT1 通过靶向 miR-320a 抑制 HCC 进展。总之,本研究结果表明,NEAT1/miR-320a/LAGE3 轴参与 HCC 的发生发展,并且 NEAT1 可以作为 HCC 的标志物。

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