Identification and Validation of the Hsa_circ_0001726/miR-140-3p/KRAS Axis in Hepatocellular Carcinoma Based on Microarray Analyses and Experiments.

IF 3.1 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Journal of Clinical and Translational Hepatology Pub Date : 2024-11-28 Epub Date: 2024-10-21 DOI:10.14218/JCTH.2024.00270

Xiaobin Chi, Zhijian Chen, Jianda Yu, Xiaohua Xie, Zerun Lin, Yongbiao Chen, Lizhi Lv

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引用次数: 0

Abstract

Background and aims: Hepatocellular carcinoma (HCC) is one of the most fatal malignancies. Epigenetic mechanisms have revealed that noncoding RNAs, such as microRNAs (miRNAs) and circular RNAs (circRNAs), are involved in HCC progression. This study aimed to construct a circRNA-miRNA-mRNA network in HCC and validate one axis within the network.

Methods: HCC-related transcriptome data were obtained from the Gene Expression Omnibus, and HCC-related genes were sourced from GeneCards to identify differentially expressed circRNAs and miRNAs. The targeting relationships between circRNA-miRNA and miRNA-mRNA interactions were predicted. The involvement of the hsa_circ_0001726/miR-140-3p/KRAS axis in HCC was evaluated through cellular experiments and survival analyses.

Results: We identified six differentially expressed circRNAs in HCC, which were linked to 13 miRNAs and 88 mRNAs. A network containing 34 circRNA-miRNA pairs and 194 miRNA-mRNA pairs was constructed. Cell proliferation and migration assays confirmed the role of hsa_circ_0001726 in promoting HCC progression, possibly through the miR-140-3p/KRAS axis. Survival analysis verified that hsa_circ_0001726 was a prognostic factor for overall survival in patients with HCC. The hsa_circ_0001726/miR-140-3p/KRAS axis also mediates lenvatinib resistance in HCC cells.

Conclusions: The HCC circRNA/miRNA/mRNA network provides new insights into the post-transcriptional regulatory mechanism of HCC. The hsa_circ_0001726/miR-140-3p/KRAS axis is involved in HCC progression and lenvatinib resistance.

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基于芯片分析和实验的肝细胞癌中 Hsa_circ_0001726/miR-140-3p/KRAS 轴的鉴定和验证

背景和目的：肝细胞癌（HCC）是最致命的恶性肿瘤之一。表观遗传学机制揭示，微RNA（miRNA）和环状RNA（circRNA）等非编码RNA参与了HCC的进展。本研究旨在构建HCC中的circRNA-miRNA-mRNA网络，并验证该网络中的一个轴。方法：从基因表达总库（Gene Expression Omnibus）中获取HCC相关转录组数据，并从GeneCards中获取HCC相关基因，以鉴定差异表达的circRNA和miRNA。预测了circRNA-miRNA和miRNA-mRNA相互作用的靶向关系。通过细胞实验和生存分析评估了hsa_circ_0001726/miR-140-3p/KRAS轴在HCC中的参与情况：结果：我们发现了 6 个在 HCC 中差异表达的 circRNA，它们与 13 个 miRNA 和 88 个 mRNA 相关联。我们构建了一个包含 34 个 circRNA-miRNA 对和 194 个 miRNA-mRNA 对的网络。细胞增殖和迁移试验证实了 hsa_circ_0001726 可能通过 miR-140-3p/KRAS 轴在促进 HCC 进展中的作用。生存分析证实，hsa_circ_0001726是影响HCC患者总生存期的预后因素。hsa_circ_0001726/miR-140-3p/KRAS轴还介导了来伐替尼对HCC细胞的耐药性：结论：HCC circRNA/miRNA/mRNA网络为了解HCC转录后调控机制提供了新的视角。hsa_circ_0001726/miR-140-3p/KRAS轴参与了HCC进展和来伐替尼耐药。

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来源期刊

Journal of Clinical and Translational Hepatology GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

6.40

自引率

2.80%

发文量

496