Department of Gastroenterology, the Second Affiliated Hospital of Nanchang University, Nanchang, China.
RNA Biol. 2020 Mar;17(3):381-394. doi: 10.1080/15476286.2019.1708547. Epub 2020 Jan 2.
LncRNA ANCR plays important roles in the modulation of epithelial mesenchymal transition (EMT) and tumour metastasis in many tumours. However, the role of ANCR in regulating hepatocellular carcinoma (HCC) metastasis is still not known. The current study aims to investigate the underlying mechanism for tumour oncogenesis of ANCR in HCC metastasis. HCC cell proliferation and migration/invasion were measured by MTT and Transwell assays. Xenograft model was established to determine the effect of ANCR on HCC growth and metastasis. ChIP assay was used to detect the H3 and H4 histone acetylation levels at the ANCR promoter region. RNA pull-down and RIP assay was performed to analyse the relationship between ANCR and heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1). Dual-luciferase reporter gene assay was conducted to determine the interaction between ANCR and miR-140-3p. The results indicated that ANCR was highly expressed in HCC tissues and cells, which promoted the proliferation and migration/invasion of HCC cells. experiments showed interfering ANCR suppressed the growth and metastasis of HCC. H3/H4 histone acetylation levels at the ANCR promoter region were elevated in HCC tissues and cells, and interfering histone deacetylases 3 (HDAC3) significantly up-regulated ANCR expression. ANCR could bind to HNRNPA1, and promoted the expression of HNRNPA1 through regulating its degradation. In addition, ANCR upregulated the expression of HNRNPA1 through sponging miR-140-3p. Finally, we found that ANCR promoted the EMT and invasion/migration of HCC cells through regulating HNRNPA1. In conclusion, ANCR promoted HCC metastasis by upregulating HNRNPA1, inhibiting HNRNPA1 degradation and sponging miR-140-3p.
长链非编码 RNA（lncRNA）ANCR 在许多肿瘤中上皮间质转化（EMT）和肿瘤转移的调节中发挥重要作用。然而，ANCR 在调节肝细胞癌（HCC）转移中的作用尚不清楚。本研究旨在探讨 ANCR 在 HCC 转移中肿瘤发生的潜在机制。通过 MTT 和 Transwell 测定法测量 HCC 细胞的增殖和迁移/侵袭。建立异种移植模型以确定 ANCR 对 HCC 生长和转移的影响。ChIP 测定法用于检测 ANCR 启动子区域的 H3 和 H4 组蛋白乙酰化水平。RNA 下拉和 RIP 测定法用于分析 ANCR 与异质核核糖核蛋白 A1（HNRNPA1）之间的关系。双荧光素酶报告基因测定法用于确定 ANCR 与 miR-140-3p 之间的相互作用。结果表明，ANCR 在 HCC 组织和细胞中高表达，促进了 HCC 细胞的增殖和迁移/侵袭。实验表明，干扰 ANCR 抑制了 HCC 的生长和转移。HCC 组织和细胞中 ANCR 启动子区域的 H3/H4 组蛋白乙酰化水平升高，干扰组蛋白去乙酰化酶 3（HDAC3）可显著上调 ANCR 表达。ANCR 可以与 HNRNPA1 结合，并通过调节其降解来促进 HNRNPA1 的表达。此外，ANCR 通过海绵 miR-140-3p 上调 HNRNPA1 的表达。最后，我们发现 ANCR 通过调节 HNRNPA1 促进 HCC 细胞的 EMT 和侵袭/迁移。总之，ANCR 通过上调 HNRNPA1、抑制 HNRNPA1 降解和海绵 miR-140-3p 促进 HCC 转移。
