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长链非编码 RNA NEAT1 通过海绵吸附 miR-214 促进肝癌肿瘤生长。

LncRNA NEAT1 sponges miR-214 to promoted tumor growth in hepatocellular carcinoma.

机构信息

Intervention Department, Affiliated Tumor Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, 830000, China.

Ultrasonic Department, Affiliated Tumor Hospital of Xinjiang Medical University, The First Affiliated Hospital of Xinjiang Medical University, No.137, Liyushan South Road, Xincheng District, Xinjiang Uygur Autonomous Region, Urumqi, 830054, China.

出版信息

Mamm Genome. 2022 Sep;33(3):525-533. doi: 10.1007/s00335-022-09952-1. Epub 2022 Mar 31.

Abstract

Live cancer is the sixth most prevalent diagnosed malignant tumor and the fourth leading cause of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) is the main histological type of liver cancer. Here, we attempt to evaluate the role of long non coding RNA NEAT1 in HCC, and explore its potential mechanism in this disease. Initially, we detected the expression of NEAT1 in HCC cell lines (SMMC-7721 and Huh7 cells) using qRT-PCR. Then we transfected si-NC or si-NEAT1 into SMMC-7721 and Huh7 cells by RNA interference. CCK-8 assay, transwell assay, flow cytometry, qRT-PCR and western blotting were used to evaluate the role of NEAT1 in the biological behavior of SMMC-7721 and Huh7 cells. The rescue experiment, RIP assay and MeRIP were devoted to the underlying mechanism. NEAT1 expression level was significantly elevated in SMMC-7721 and Huh7 cells. Knockdown of NEAT1 inhibited proliferation and migration, induced apoptosis of HCC cell lines. NEAT1 serves as a sponge for miR-214. Besides, PSMB8 was a direct target of miR-214. Furthermore, ALKBH5 could up-regulate NEAT1 expression by inhibiting m6A enrichment. ALKBH5-induced NEAT1 promoted cell proliferation and migration of HCC by sponging miR-214 in vitro, which may provide a potential therapeutic target for HCC.

摘要

原发性肝癌是全球第六大常见恶性肿瘤,也是癌症相关死亡的第四大主要原因。肝细胞癌(HCC)是肝癌的主要组织学类型。在这里,我们试图评估长链非编码 RNA NEAT1 在 HCC 中的作用,并探讨其在该疾病中的潜在机制。首先,我们通过 qRT-PCR 检测了 HCC 细胞系(SMMC-7721 和 Huh7 细胞)中 NEAT1 的表达。然后,我们通过 RNA 干扰将 si-NC 或 si-NEAT1 转染到 SMMC-7721 和 Huh7 细胞中。CCK-8 测定、transwell 测定、流式细胞术、qRT-PCR 和 Western blot 用于评估 NEAT1 在 SMMC-7721 和 Huh7 细胞生物学行为中的作用。挽救实验、RIP 测定和 MeRIP 用于研究潜在的机制。在 SMMC-7721 和 Huh7 细胞中,NEAT1 的表达水平显著升高。敲低 NEAT1 抑制 HCC 细胞系的增殖和迁移,诱导细胞凋亡。NEAT1 作为 miR-214 的海绵。此外,PSMB8 是 miR-214 的直接靶标。此外,ALKBH5 通过抑制 m6A 富集来上调 NEAT1 的表达。ALKBH5 诱导的 NEAT1 通过在体外海绵吸附 miR-214 促进 HCC 细胞的增殖和迁移,这可能为 HCC 提供了一个潜在的治疗靶点。

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