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羟基酸氧化酶 2(HAO2)抑制肝癌的致瘤性,并受 miR-615-5p 的负调控。

Hydroxyacid Oxidase 2 (HAO2) Inhibits the Tumorigenicity of Hepatocellular Carcinoma and Is Negatively Regulated by miR-615-5p.

机构信息

Department of Gastroenterology, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, China.

Xinxiang Medical University, Xinxiang, 453000 Henan, China.

出版信息

J Immunol Res. 2022 Apr 28;2022:5003930. doi: 10.1155/2022/5003930. eCollection 2022.

DOI:10.1155/2022/5003930
PMID:35528616
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9071856/
Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is the sixth most common kind of cancer worldwide and the third leading cause of cancer mortality. Although a few studies have shown that hydroxyacid oxidase 2 (HAO2) may prevent HCC development, the molecular mechanism is unclear.

METHODS

We examined the levels of HAO2 expression in 23 pairs of HCC/paracancerous tissues by quantitative real-time polymerase chain reaction (qRT-PCR) and evaluated HAO2's expression in The Cancer Genome Atlas (TCGA) database. Furthermore, we examined the biological activity of HAO2 utilizing cell-based functional assays. Additionally, we evaluated the relationship between miR-615-5p and HAO2 in Hep3B cells using a dual-luciferase reporter system and assessed the downstream regulatory mechanisms of miR-615-5p on HAO2. Finally, the nude mice tumor formation experiment was used to determine the impact of HAO2 on the tumorigenicity of HCC cells.

RESULTS

HAO2 expression was considerably underexpression in HCC tissues and cells, and patients with low HAO2 expression had poorer disease-free survival. Inhibition of cell proliferation, migration, and invasion was observed when HAO2 was overexpressed. miR-615-5p had a negative relation with HAO2, and miR-615-5p restored HAO2's biological activity in HCC cells. Additionally, the tumor volume and weight were considerably reduced in the OV-HAO2 group compared to the OV-NC group.

CONCLUSION

HAO2 was found to be underexpressed in HCC tissues and cells, and HAO2 overexpression inhibited HCC cell motility, which was negatively regulated by miR-615-5p. Exogenous expression of HAO2 reduced the tumorigenicity of HCC cells in vivo in nude mice.

摘要

背景

肝细胞癌(HCC)是全球第六种最常见的癌症,也是癌症死亡的第三大主要原因。尽管有几项研究表明羟基酸氧化酶 2(HAO2)可能预防 HCC 的发生,但分子机制尚不清楚。

方法

我们通过定量实时聚合酶链反应(qRT-PCR)检测了 23 对 HCC/癌旁组织中 HAO2 的表达水平,并评估了 TCGA 数据库中 HAO2 的表达情况。此外,我们利用基于细胞的功能测定法来检测 HAO2 的生物学活性。此外,我们使用双荧光素酶报告系统评估了 miR-615-5p 与 Hep3B 细胞中 HAO2 之间的关系,并评估了 miR-615-5p 对 HAO2 的下游调节机制。最后,使用裸鼠肿瘤形成实验来确定 HAO2 对 HCC 细胞致瘤性的影响。

结果

HAO2 在 HCC 组织和细胞中表达明显下调,低 HAO2 表达的患者无病生存期较差。当 HAO2 过表达时,观察到细胞增殖、迁移和侵袭受到抑制。miR-615-5p 与 HAO2 呈负相关,miR-615-5p 恢复了 HCC 细胞中 HAO2 的生物学活性。此外,与 OV-NC 组相比,OV-HAO2 组的肿瘤体积和重量明显减小。

结论

HAO2 在 HCC 组织和细胞中表达下调,HAO2 过表达抑制 HCC 细胞的运动性,miR-615-5p 对其起负调控作用。外源性表达 HAO2 可降低裸鼠体内 HCC 细胞的致瘤性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3d3/9071856/38de109e237d/JIR2022-5003930.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3d3/9071856/c6f4eacbd748/JIR2022-5003930.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3d3/9071856/bf913922aef4/JIR2022-5003930.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3d3/9071856/7e98cbf0d6ae/JIR2022-5003930.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3d3/9071856/3a6d0c741ee5/JIR2022-5003930.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3d3/9071856/38de109e237d/JIR2022-5003930.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3d3/9071856/c6f4eacbd748/JIR2022-5003930.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3d3/9071856/bf913922aef4/JIR2022-5003930.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3d3/9071856/7e98cbf0d6ae/JIR2022-5003930.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3d3/9071856/3a6d0c741ee5/JIR2022-5003930.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3d3/9071856/38de109e237d/JIR2022-5003930.005.jpg

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