p62 acts as an oncogene and is targeted by miR-124-3p in glioma

Danni Deng; Kaiming Luo; Hongmei Liu; Xichen Nie; Lian Xue; Rong Wang; Yuan Xu; Jun Cui; Naiyuan Shao; Feng Zhi

doi:10.1186/s12935-019-1004-x

p62 acts as an oncogene and is targeted by miR-124-3p in glioma

Cancer Cell Int. 2019 Nov 6:19:280. doi: 10.1186/s12935-019-1004-x. eCollection 2019.

Authors

Danni Deng^#^{1

2}, Kaiming Luo^#^{2

3}, Hongmei Liu^#⁴, Xichen Nie⁵, Lian Xue^{1

2}, Rong Wang^{1

2}, Yuan Xu^{1

2}, Jun Cui⁵, Naiyuan Shao¹, Feng Zhi^{1

2}

Affiliations

¹ 1Department of Neurosurgery, The First People's Hospital of Changzhou, #185 Juqian Road, Changzhou, Jiangsu China.
² 2Modern Medical Research Center, The Third Affiliated Hospital of Soochow University, #185 Juqian Road, Changzhou, Jiangsu China.
³ 3Department of Endocrinology, The First People's Hospital of Changzhou, Changzhou, Jiangsu China.
⁴ 4School of Biological Science and Medical Engineering, Beihang University, #37 Xueyuan Road, Beijing, China.
⁵ 5MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, #135 Xingangxi Road, Guangzhou, China.

^# Contributed equally.

Abstract

Background: Glioma is the most common central nervous system (CNS) tumour. p62, an important autophagy adaptor, plays a crucial role in cancer. However, the role of p62 in the progression of glioma is poorly characterized.

Methods: We examined the expression of p62 in glioma tissues and cell lines. Then we investigated the function of p62 in vitro, and clarified the mechanism underlying the regulation of p62 expression.

Results: We revealed that p62 was upregulated at both the mRNA and protein levels in human glioma tissues irrelevant to isocitrate dehydrogenase (IDH) status. Then, we found that overexpression of p62 promoted glioma progression by promoting proliferation, migration, glycolysis, temozolomide (TMZ) resistance and nuclear factor κB (NF-κB) signalling pathway, and repressing autophagic flux and reactive oxygen species (ROS) in vitro. In accordance with p62 overexpression, knockdown of p62 exerted anti-tumour effects in glioma cells. Subsequently, we demonstrated that miR-124-3p directly targeted the 3'-UTR of p62 mRNA, leading to the downregulation of p62. Finally, we found that p62 function could be partially reversed by miR-124-3p overexpression.

Conclusions: Our results demonstrate that p62 can be targeted by miR-124-3p and acts as an oncogene in glioma, suggesting the potential value of p62 as a novel therapeutic target for glioma.

Keywords: Glycolysis; Migration; Proliferation; TMZ resistance; miR-124-3p; p62.