Circular RNA ACVR2A promotes the progression of hepatocellular carcinoma through mir-511-5p targeting PI3K-Akt signaling pathway

IF 27.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Cancer Pub Date : 2024-08-06 DOI:10.1186/s12943-024-02074-z
Du Fei, Fang Wang, Yaohui Wang, Ji Chen, Shendong Chen, Lianpeng Fan, Luhan Yang, Qingyi Ren, Suwit Duangmano, Fukuan Du, Hao Liu, Jie Zhou, Jing Sheng, Yueshui Zhao, Xu Wu, Mingxing Li, Zhangang Xiao, Zhuo Zhang, Xian Jiang
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Abstract

Circular RNA (circRNA) is thought to mediate the occurrence and development of human cancer and usually acts as a tiny RNA (miRNA) sponge to regulate downstream gene expression. However, it is not clear whether and how circACVR2A (hsa_circ_0001073) is involved in the progression of HCC. The purpose of this study is to clarify the potential role and molecular mechanism of circACVR2A in regulating the progression of hepatocellular carcinoma cells (HCC). The abundance of related proteins in circACVR2A, microRNA (miR511-5p) and PI3K-Akt signaling pathway was determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) or Western blotting. Cell viability, invasion and apoptosis were analyzed by CCK-8, Transwell analysis and Tunel staining, respectively. The interaction between circACVR2A and microRNA was evaluated by double luciferase reporter gene assay. The results showed that circACVR2A was highly expressed in hepatocellular carcinoma cell lines. Our in vivo and in vitro data showed that circACVR2A promoted the proliferation, migration and invasion of HCC. In terms of mechanism, we found that circACVR2A can directly interact with miR511-5p and act as a miRNA sponge to regulate the expression of related proteins in PI3K-Akt signaling pathway. In HCC, circACVR2A can mediate miR-511-5p/mRNA network to activate PI3K signal pathway. This shows that the molecular regulatory network with circACVR2A as the core is a new potential target for diagnosis and treatment of hepatocellular carcinoma.
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环状 RNA ACVR2A 通过 mir-511-5p 靶向 PI3K-Akt 信号通路促进肝细胞癌的进展
环状 RNA(circRNA)被认为介导人类癌症的发生和发展,通常作为微小 RNA(miRNA)海绵调控下游基因的表达。然而,尚不清楚 circACVR2A (hsa_circ_0001073) 是否以及如何参与 HCC 的进展。本研究旨在阐明 circACVR2A 在调控肝癌细胞(HCC)进展中的潜在作用和分子机制。研究采用定量逆转录酶聚合酶链反应(RT-PCR)或 Western 印迹法测定了 circACVR2A、microRNA(miR511-5p)和 PI3K-Akt 信号通路中相关蛋白的丰度。细胞活力、侵袭和凋亡分别通过 CCK-8、Transwell 分析和 Tunel 染色进行分析。通过双荧光素酶报告基因实验评估了 circACVR2A 与 microRNA 之间的相互作用。结果显示,circACVR2A 在肝癌细胞系中高表达。我们的体内和体外数据显示,circACVR2A 促进了 HCC 的增殖、迁移和侵袭。在机制方面,我们发现 circACVR2A 可直接与 miR511-5p 相互作用,并作为 miRNA 海绵调控 PI3K-Akt 信号通路中相关蛋白的表达。在 HCC 中,circACVR2A 可介导 miR-511-5p/mRNA 网络激活 PI3K 信号通路。这表明,以 circACVR2A 为核心的分子调控网络是诊断和治疗肝细胞癌的潜在新靶点。
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来源期刊
Molecular Cancer
Molecular Cancer 医学-生化与分子生物学
CiteScore
54.90
自引率
2.70%
发文量
224
审稿时长
2 months
期刊介绍: Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer. The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies. Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.
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