Knockdown of hsa_circ_0102231 Impedes the Progression of Liver Cancer through the miR-873-SOX4 Axis.

IF 3.8 4区医学 Q2 GENETICS & HEREDITY

Current gene therapy Pub Date : 2024-07-03 DOI:10.2174/0115665232301878240627051455

Jingyu Qian, Banghong Jiang, Zhongqiang Qin, Yulin Tan

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引用次数: 0

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most intractable tumors in the world due to its high rate of recurrence and heterogeneity.

Aim: The objective of this study was to investigate the role of circular RNA 0102231 (hsa_circ_ 0102231) in the progression of liver cancer.

Methods: In this study, quantitative polymerase chain reaction experiments were performed to quantify the hsa_circ_0102231 level in different liver cancer cell lines. Bioinformatics analysis, as well as a dual-luciferase reporter and RNA pull-down assay, were used to identify putative hsa_circ_ 0102231 downstream targets. Colony formation and CCK8 assays were utilized to examine cell proliferation, whereas Transwell assays were employed to monitor cell migration. Lastly, the role of hsa_circ_0102231 in liver cancer was assessed in a subcutaneous xenograft model.

Results: The expression of hsa_circ_0102231 increased significantly in HepG2 and Huh-7 cells compared with controls, and hsa_circ_0102231 knockdown inhibited cell proliferation and migration in vitro and in vivo. Bioinformatics analysis, as well as a dual-luciferase reporter and RNA pulldown assay, revealed that miR-873 and SOX4 were hsa_circ_0102231 downstream targets. miR-873 inhibition or SOX4 overexpression rescued the proliferation and migration of HepG2 and Huh-7 cells after hsa_circ_0102231 knockdown. Furthermore, SOX4 overexpression reversed the miR-873-induced inhibition of cell migration and proliferation in vitro.

Conclusion: These results show that hsa_circ_0102231 knockdown impedes the progression of liver cancer by regulating the miR-873/SOX4 axis. However, further studies are needed to determine whether hsa_circ_0102231 may be a therapeutic target in liver cancer.

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敲除 hsa_circ_0102231 会通过 miR-873-SOX4 轴阻碍肝癌的进展

背景：目的：本研究旨在探讨环状 RNA 0102231（hsa_circ_ 0102231）在肝癌进展中的作用：方法：本研究通过定量聚合酶链反应实验来定量检测不同肝癌细胞系中的 hsa_circ_0102231 水平。生物信息学分析以及双荧光素酶报告和 RNA 下拉实验被用来确定 hsa_circ_0102231 的推定下游靶点。利用集落形成和CCK8检测法检查细胞增殖，而利用Transwell检测法监测细胞迁移。最后，在皮下异种移植模型中评估了 hsa_circ_0102231 在肝癌中的作用：结果：与对照组相比，hsa_circ_0102231在HepG2和Huh-7细胞中的表达明显增加，敲除hsa_circ_0102231可抑制体外和体内细胞的增殖和迁移。生物信息学分析以及双荧光素酶报告和 RNA pulldown 分析显示，miR-873 和 SOX4 是 hsa_circ_0102231 的下游靶标。此外，SOX4 的过表达逆转了 miR-873 诱导的体外细胞迁移和增殖抑制：这些结果表明，敲除 hsa_circ_0102231 可通过调节 miR-873/SOX4 轴阻碍肝癌的进展。然而，要确定 hsa_circ_0102231 是否可能成为肝癌的治疗靶点，还需要进一步的研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current gene therapy 医学-遗传学

CiteScore

6.70

自引率

2.80%

发文量

期刊介绍： Current Gene Therapy is a bi-monthly peer-reviewed journal aimed at academic and industrial scientists with an interest in major topics concerning basic research and clinical applications of gene and cell therapy of diseases. Cell therapy manuscripts can also include application in diseases when cells have been genetically modified. Current Gene Therapy publishes full-length/mini reviews and original research on the latest developments in gene transfer and gene expression analysis, vector development, cellular genetic engineering, animal models and human clinical applications of gene and cell therapy for the treatment of diseases. Current Gene Therapy publishes reviews and original research containing experimental data on gene and cell therapy. The journal also includes manuscripts on technological advances, ethical and regulatory considerations of gene and cell therapy. Reviews should provide the reader with a comprehensive assessment of any area of experimental biology applied to molecular medicine that is not only of significance within a particular field of gene therapy and cell therapy but also of interest to investigators in other fields. Authors are encouraged to provide their own assessment and vision for future advances. Reviews are also welcome on late breaking discoveries on which substantial literature has not yet been amassed. Such reviews provide a forum for sharply focused topics of recent experimental investigations in gene therapy primarily to make these results accessible to both clinical and basic researchers. Manuscripts containing experimental data should be original data, not previously published.