综合分析 CTNNB1 突变肝细胞癌中的 ncRNA 发现 miR-205-5p 和 miR-3940-3p 轴。

IF 4 3区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Digestive and Liver Disease Pub Date : 2025-01-01 Epub Date: 2024-06-25 DOI:10.1016/j.dld.2024.06.001

Haibin Zhang, Guoqing Zhang, Siyu Lu, Xiaolu Zhang, Jingya Yu

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引用次数: 0

摘要

背景：Catenin beta 1（CTNNB1）突变是肝细胞癌（HCC）进展过程中最常见的突变之一。然而，CTNNB1 突变与 HCC 之间的关系仍存在争议：方法：从HCC患者中采集了5份CTNNB1野生型肿瘤样本和3份CTNNB1突变肿瘤样本，进行全转录组测序。通过 qPCR 验证了 48 例 HCC 肿瘤中的部分 ncRNA 和 mRNA。通过转染 miRNA 的模拟物和抑制剂，在 HCC 细胞中验证了选定的 ncRNA 调控轴：结果：构建了一个差异表达（DE）lncRNA/circRNA-miRNA-mRNA网络，以探讨CTNNB1突变对ncRNA调控的影响。为验证测序结果，在 RNA 表达水平上验证了 TXNRD1、CES1、MATN2、SERPINA5、lncRNA STAT4-210、hsa_circ_0007824、hsa_circ_0008234、hsa-miR-205-5p 和 hsa-miR-199a-5p。GLIS3-209/circ_0085440-miR-205-5p-GHRHR和WNK2-213-miR-3940-3p-LY6E在表达水平上得到验证，并被证明分别抑制和促进细胞增殖：该研究证实了CTNNB1突变相关的ncRNA调控轴在HCC细胞增殖中发挥着不同的作用，为CTNNB1在HCC中的争议性作用提供了新的见解。

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Integrated analysis of ncRNA in hepatocellular carcinoma with CTNNB1 mutations reveals miR-205-5p and miR-3940-3p Axes.

Background: Catenin beta 1 (CTNNB1) mutations are one of the most common mutations involved in hepatocellular carcinoma (HCC) progression. However, the association between CTNNB1 mutations and HCC remains controversial.

Methods: Five tumor samples with wild-type CTNNB1 and three tumor samples with CTNNB1 mutations were collected from patients with HCC for whole transcriptome sequencing. Selected ncRNAs and mRNAs were validated by qPCR in 48 HCC tumors. Selected ncRNA regulatory axes were verified in HCC cells by transfecting mimics and inhibitors of miRNA.

Results: A network of differentially expressed (DE) lncRNA/circRNA-miRNA-mRNA was constructed to explore the effects of CTNNB1 mutations on ncRNA regulation. TXNRD1, CES1, MATN2, SERPINA5, lncRNA STAT4-210, hsa_circ_0007824, hsa_circ_0008234, hsa-miR-205-5p and hsa-miR-199a-5p were verified at the RNA expression level to validate the sequencing results. The down-up-down axes GLIS3-209/circ_0085440-miR-205-5p-GHRHR and WNK2-213-miR-3940-3p-LY6E were verified at the expression level, and proved to inhibit and promote cell proliferation, respectively.

Conclusion: This study demonstrated CTNNB1 mutations associated ncRNA regulatory axes playing different roles in HCC cell proliferation, providing novel insights into the controversial role of CTNNB1 in HCC.

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来源期刊

Digestive and Liver Disease 医学-胃肠肝病学

CiteScore

6.10

自引率

2.20%

发文量

632

审稿时长

19 days

期刊介绍： Digestive and Liver Disease is an international journal of Gastroenterology and Hepatology. It is the official journal of Italian Association for the Study of the Liver (AISF); Italian Association for the Study of the Pancreas (AISP); Italian Association for Digestive Endoscopy (SIED); Italian Association for Hospital Gastroenterologists and Digestive Endoscopists (AIGO); Italian Society of Gastroenterology (SIGE); Italian Society of Pediatric Gastroenterology and Hepatology (SIGENP) and Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD). Digestive and Liver Disease publishes papers on basic and clinical research in the field of gastroenterology and hepatology. Contributions consist of: Original Papers Correspondence to the Editor Editorials, Reviews and Special Articles Progress Reports Image of the Month Congress Proceedings Symposia and Mini-symposia.