Long Non-Coding RNA H19 Regulates Glioma Cell Growth and Metastasis via miR-200a-Mediated CDK6 and ZEB1 Expression.

Xuezhu Chen,Yang Yang,Chenghai Zuo,Jishu Xian,Xuejiao Lei,Yuhong Li,Hua Feng,Ju Wang,Ning Mu,Jianmin Zhang,Tunan Chen,Kang Ma,Rongrui Tang,Shi Wang,Chuanyan Yang,Kaiyuan Zhang

doi:10.3389/fonc.2021.757650

Abstract

Long non-coding RNAs (lncRNAs) serve essential roles on various biological functions. Previous studies have indicated that lncRNAs are involved in the occurrence, growth and infiltration of brain tumors. LncRNA H19 is key regulator in the pathogenesis of gliomas, but the underlying mechanisms of H19-regulated tumor progression remain unknown. Therefore, we investigated the effects and mechanism of action of lncRNA H19 on the homeostasis of glioma cells. As a novel oncogenic factor, up-regulation of H19 was able to promote the proliferation of glioma cells by targeting miR-200a. Furthermore, elevated miR-200a levels could reverse H19-induced cell growth and metastasis. Overexpression of miR-200a could significantly suppress the proliferation, migration and invasion of glioma cells. These biological behavior changes in glioma cells were dependent on the binding to potential target genes including CDK6 and ZEB1. CDK6 could promote cell proliferation and its expression was remarkably increased in glioma. In addition, up-regulation of miR-200a lead to reduction of CDK6 expression and inhibit the proliferation of glioma cells. ZEB1 could be a putative target gene of miR-200a in glioma cells. Thus, miR-200a might suppress cell invasion and migration through down-regulating ZEB1. Moreover, overexpression of miR-200a resulted in down-regulation of ZEB1 and further inhibited malignant phenotype of glioma cells. In summary, our findings suggested that the expression of H19 was elevated in glioma, which could promote the growth, invasion and migration of tumor cells via H19/miR-200a/CDK6/ZEB1 axis. This novel signaling pathway may be a promising candidate for the diagnosis and targeted treatment of glioma.

Highlights

Glioma is a common type of malignancy in brain
Up-Regulation of Long non-coding RNAs (lncRNAs) H19 Is Detected in Glioma Tissues and Cell Lines
To investigate the expression of lncRNA H19 in glioma, the results of RT-qPCR confirmed that the RNA levels of H19 were notably upregulated in tumor samples compared with normal control (Figure 1A)

Summary

Introduction

Glioma is a common type of malignancy in brain. It is characterized by poor prognosis and accounts for >90% of all intracranial tumors [1, 2]. The diagnosis and treatment of glioma have been remarkably improved. The detailed molecular mechanisms involved in the progression of glioma remain unclear, so the prevention and treatment of this disease are still not satisfactory [3]. It is well established that most tumors are highly polygenic, and proliferation and invasion of tumor cells are associated with the up-regulation of oncogenes or down-regulation of tumor suppressor genes [4, 5]. A better understanding of the molecular mechanisms involved in the pathogenesis of glioma is essential for the diagnosis, treatment and prognosis of this disease

Methods

Results

Conclusion