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长链非编码 RNA ANCR 通过上调 HNRNPA1 表达促进肝癌转移。

LncRNA ANCR promotes hepatocellular carcinoma metastasis through upregulating HNRNPA1 expression.

机构信息

Department of Gastroenterology, the Second Affiliated Hospital of Nanchang University, Nanchang, China.

出版信息

RNA Biol. 2020 Mar;17(3):381-394. doi: 10.1080/15476286.2019.1708547. Epub 2020 Jan 2.


DOI:10.1080/15476286.2019.1708547
PMID:31868085
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6999620/
Abstract

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.

摘要

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。

相似文献

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引用本文的文献

[1]
The epigenetic regulatory network of long noncoding RNAs in hepatocellular carcinoma.

Genes Dis. 2025-1-20

[2]
Downregulation of hnRNPA1 inhibits hepatocellular carcinoma cell progression by modulating alternative splicing of ZNF207 exon 9.

Front Oncol. 2025-1-6

[3]
Epigenetic modifications involving ncRNAs in digestive system cancers: focus on histone modification.

Clin Epigenetics. 2024-11-19

[4]
[ gene is highly expressed in colorectal cancer: its prognostic implications and potential as a therapeutic target].

Nan Fang Yi Ke Da Xue Xue Bao. 2024-9-20

[5]
Dynamic role of exosomal long non-coding RNA in liver diseases: pathogenesis and diagnostic aspects.

Hepatol Int. 2024-12

[6]
hnRNPA1 promotes the metastasis and proliferation of gastric cancer cells through WISP2-guided Wnt/β-catenin signaling pathway.

Discov Oncol. 2024-9-19

[7]
Epigenetics in the formation of pathological aggregates in amyotrophic lateral sclerosis.

Front Mol Neurosci. 2024-9-3

[8]
Diagnostic model for hepatocellular carcinoma using small extracellular vesicle-propagated miRNA signatures.

Front Mol Biosci. 2024-6-28

[9]
LncRNA ZFAS1 regulates ATIC transcription and promotes the proliferation and migration of hepatocellular carcinoma through the PI3K/AKT signaling pathway.

J Cancer Res Clin Oncol. 2024-7-13

[10]
New evidence for a role of DANCR in cancers: a comprehensive review.

J Transl Med. 2024-6-14

本文引用的文献

[1]
DANCR promotes HCC progression and regulates EMT by sponging miR-27a-3p via ROCK1/LIMK1/COFILIN1 pathway.

Cell Prolif. 2019-4-30

[2]
LncRNA DCST1-AS1 functions as a competing endogenous RNA to regulate FAIM2 expression by sponging miR-1254 in hepatocellular carcinoma.

Clin Sci (Lond). 2019-1-30

[3]
lncRNA MALAT1 binds chromatin remodeling subunit BRG1 to epigenetically promote inflammation-related hepatocellular carcinoma progression.

Oncoimmunology. 2018-10-16

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Analysis of prognostic factors of more/equal to10 years of survival for liver cancer patients after liver transplantation.

J Cancer Res Clin Oncol. 2018-9-26

[5]
Long noncoding RNA ANCR suppresses bone formation of periodontal ligament stem cells via sponging miRNA-758.

Biochem Biophys Res Commun. 2018-6-22

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High expression of hnRNPA1 promotes cell invasion by inducing EMT in gastric cancer.

Oncol Rep. 2018-2-16

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Cancer statistics, 2018.

CA Cancer J Clin. 2018-1-4

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Long non-coding RNA CCAL promotes hepatocellular carcinoma progression by regulating AP-2α and Wnt/β-catenin pathway.

Int J Biol Macromol. 2017-12-22

[9]
lncRNA MIAT promotes proliferation and invasion of HCC cells via sponging miR-214.

Am J Physiol Gastrointest Liver Physiol. 2017-11-2

[10]
LncRNA ANCR down-regulation promotes TGF-β-induced EMT and metastasis in breast cancer.

Oncotarget. 2017-6-27

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