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hsa_circ_0008305通过调控AKR1C3的表达及吸附miR-379-5p促进肝细胞癌的恶性进展。

hsa_circ_0008305 facilitates the malignant progression of hepatocellular carcinoma by regulating AKR1C3 expression and sponging miR-379-5p.

作者信息

Huang Shenglan, Liu Kan, Xu Yongkan, Wang Hua, Fu Shumin, Wu Jianbing

机构信息

Department of Oncology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1, Minde Road, Nanchang, 330000, Jiangxi Province, P.R. China.

出版信息

Sci Rep. 2025 Jan 8;15(1):1309. doi: 10.1038/s41598-025-85737-1.

Abstract

Circular RNAs (circRNAs) are widely involved in diverse biological processes of cancers. Nonetheless, the potential function of hsa_circ_0008305 in hepatocellular carcinoma (HCC) remains largely unknown. This study aims to elucidate the role and underlying mechanism of hsa_circ_0008305 in HCC. Our findings reveal that the novel circRNA hsa_circ_0008305 (circPTK2) is significantly upregulated in HCC tissues, with its elevated expression being positively correlated with advanced tumor T stage and vascular invasion. The circular characteristics and subcellular localization of hsa_circ_0008305 was determined by RNase R treatment and RNA nucleocytoplasmic separation. Further functional assays, including CCK8, EdU, colony formation assays, scratch-healing, transwell assays, and Xenograft tumor models were conducted to explore the biological functions of circPTK2. The regulatory mechanisms of circPTK2 were elucidated through RNA sequencing, enrichment analysis, and dual luciferase reporter assay. Our findings indicate that circPTK2 is stably localized in the cytoplasm. Functionally, circPKT2 promoted the HCC cells proliferation, migration, and invasion both in vitro and vivo. Mechanistically, circPTK2 was found to positively regulates the expression of AKR1C3 by acting as a sponge for miR-379-5p. Inhibition of miR-379-5p significantly mitigates the biological effects induced by circPTK2. AKR1C3 is identified as a direct target of miR-379-5p, and silencing AKR1C3 overturns the promotion progression effects of miR-379-5p inhibitor. In conclusion, our results revealed that circPTK2 facilitates the malignant progression of HCC via sponging miR-379-5p to up-regulate AKR1C3 expression.

摘要

环状RNA(circRNAs)广泛参与癌症的多种生物学过程。然而,hsa_circ_0008305在肝细胞癌(HCC)中的潜在功能在很大程度上仍不清楚。本研究旨在阐明hsa_circ_0008305在HCC中的作用及其潜在机制。我们的研究结果显示,新型环状RNA hsa_circ_0008305(circPTK2)在HCC组织中显著上调,其表达升高与肿瘤T分期进展和血管侵犯呈正相关。通过RNase R处理和RNA核质分离确定了hsa_circ_0008305的环状特征和亚细胞定位。进一步进行了功能实验,包括CCK8、EdU、集落形成实验、划痕愈合实验、transwell实验和异种移植肿瘤模型,以探究circPTK2的生物学功能。通过RNA测序、富集分析和双荧光素酶报告基因实验阐明了circPTK2的调控机制。我们的研究结果表明,circPTK2稳定定位于细胞质中。在功能上,circPKT2在体外和体内均促进HCC细胞的增殖、迁移和侵袭。机制上,发现circPTK2通过作为miR-379-5p的海绵来正向调节AKR1C3的表达。抑制miR-379-5p可显著减轻circPTK2诱导的生物学效应。AKR1C3被确定为miR-379-5p的直接靶点,沉默AKR1C3可逆转miR-379-5p抑制剂的促进展作用。总之,我们的结果表明,circPTK2通过海绵吸附miR-379-5p上调AKR1C3表达,促进HCC的恶性进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/579e/11711494/a2132527a7a1/41598_2025_85737_Fig1_HTML.jpg

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