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

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Yuxuan Li, Mingchao Zhang, Xiuling Li, Yanyan Wang, Yu Wang, Yuan Li, Huihui Zhu, Hui Ding, Xiaofang Li, Suofeng Sun
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2022/5003930
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849307625940844544
author Yuxuan Li
Mingchao Zhang
Xiuling Li
Yanyan Wang
Yu Wang
Yuan Li
Huihui Zhu
Hui Ding
Xiaofang Li
Suofeng Sun
author_facet Yuxuan Li
Mingchao Zhang
Xiuling Li
Yanyan Wang
Yu Wang
Yuan Li
Huihui Zhu
Hui Ding
Xiaofang Li
Suofeng Sun
author_sort Yuxuan Li
collection DOAJ
description 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.
format Article
id doaj-art-2acd95638e194877be4d9949ec932b6f
institution Kabale University
issn 2314-7156
language English
publishDate 2022-01-01
publisher Wiley
record_format Article
series Journal of Immunology Research
spelling doaj-art-2acd95638e194877be4d9949ec932b6f2025-08-20T03:54:42ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/5003930Hydroxyacid Oxidase 2 (HAO2) Inhibits the Tumorigenicity of Hepatocellular Carcinoma and Is Negatively Regulated by miR-615-5pYuxuan Li0Mingchao Zhang1Xiuling Li2Yanyan Wang3Yu Wang4Yuan Li5Huihui Zhu6Hui Ding7Xiaofang Li8Suofeng Sun9Department of GastroenterologyXinxiang Medical UniversityDepartment of GastroenterologyDepartment of GastroenterologyXinxiang Medical UniversityDepartment of Traditional Chinese MedicineDepartment of GastroenterologyDepartment of GastroenterologyDepartment of GastroenterologyDepartment of GastroenterologyBackground. 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.http://dx.doi.org/10.1155/2022/5003930
spellingShingle Yuxuan Li
Mingchao Zhang
Xiuling Li
Yanyan Wang
Yu Wang
Yuan Li
Huihui Zhu
Hui Ding
Xiaofang Li
Suofeng Sun
Hydroxyacid Oxidase 2 (HAO2) Inhibits the Tumorigenicity of Hepatocellular Carcinoma and Is Negatively Regulated by miR-615-5p
Journal of Immunology Research
title Hydroxyacid Oxidase 2 (HAO2) Inhibits the Tumorigenicity of Hepatocellular Carcinoma and Is Negatively Regulated by miR-615-5p
title_full Hydroxyacid Oxidase 2 (HAO2) Inhibits the Tumorigenicity of Hepatocellular Carcinoma and Is Negatively Regulated by miR-615-5p
title_fullStr Hydroxyacid Oxidase 2 (HAO2) Inhibits the Tumorigenicity of Hepatocellular Carcinoma and Is Negatively Regulated by miR-615-5p
title_full_unstemmed Hydroxyacid Oxidase 2 (HAO2) Inhibits the Tumorigenicity of Hepatocellular Carcinoma and Is Negatively Regulated by miR-615-5p
title_short Hydroxyacid Oxidase 2 (HAO2) Inhibits the Tumorigenicity of Hepatocellular Carcinoma and Is Negatively Regulated by miR-615-5p
title_sort hydroxyacid oxidase 2 hao2 inhibits the tumorigenicity of hepatocellular carcinoma and is negatively regulated by mir 615 5p
url http://dx.doi.org/10.1155/2022/5003930
work_keys_str_mv AT yuxuanli hydroxyacidoxidase2hao2inhibitsthetumorigenicityofhepatocellularcarcinomaandisnegativelyregulatedbymir6155p
AT mingchaozhang hydroxyacidoxidase2hao2inhibitsthetumorigenicityofhepatocellularcarcinomaandisnegativelyregulatedbymir6155p
AT xiulingli hydroxyacidoxidase2hao2inhibitsthetumorigenicityofhepatocellularcarcinomaandisnegativelyregulatedbymir6155p
AT yanyanwang hydroxyacidoxidase2hao2inhibitsthetumorigenicityofhepatocellularcarcinomaandisnegativelyregulatedbymir6155p
AT yuwang hydroxyacidoxidase2hao2inhibitsthetumorigenicityofhepatocellularcarcinomaandisnegativelyregulatedbymir6155p
AT yuanli hydroxyacidoxidase2hao2inhibitsthetumorigenicityofhepatocellularcarcinomaandisnegativelyregulatedbymir6155p
AT huihuizhu hydroxyacidoxidase2hao2inhibitsthetumorigenicityofhepatocellularcarcinomaandisnegativelyregulatedbymir6155p
AT huiding hydroxyacidoxidase2hao2inhibitsthetumorigenicityofhepatocellularcarcinomaandisnegativelyregulatedbymir6155p
AT xiaofangli hydroxyacidoxidase2hao2inhibitsthetumorigenicityofhepatocellularcarcinomaandisnegativelyregulatedbymir6155p
AT suofengsun hydroxyacidoxidase2hao2inhibitsthetumorigenicityofhepatocellularcarcinomaandisnegativelyregulatedbymir6155p