SNHG1 promotes malignant biological behaviors of glioma cells via microRNA-154-5p/miR-376b-3p- FOXP2- KDM5B participating positive feedback loop

Journal of Experimental & Clinical Cancer Research

Qianru He¹  Yixue Xue¹  Jun Ma¹  Lianqi Shao¹  Xuelei Ruan¹  Jian Zheng²  Han Li²  Yunhui Liu²  Chunqing Yang²  Di Wang²  Xiaobai Liu²  Zhen Li² 

[1] Department of Neurobiology, College of Basic Medicine, China Medical University;Department of Neurosurgery, Shengjing Hospital of China Medical University;

关键词: Long non-coding RNA;    microRNA;    Transcription factor;    Glioma;    Oncogenes;   

DOI  :  10.1186/s13046-019-1063-9

来源: DOAJ

【 摘 要 】

Abstract Background Long non-coding RNAs has been reported in tumorigenesis and play important roles in regulating malignant behavior of cancers, including glioma. Methods According to the TCGA database, we identified SNHG1, miRNA-154-5p and miR-376b-3p whose expression were significantly changed in the glioma samples. Furthermore, we investigated SNHG1, miRNA-154-5p and miR-376b-3p expression in clinical samples and glioma cell lines using qRT-PCR analysis and the correlation between them using RNA immunoprecipitation and dual-luciferase reporter. The underlying mechanisms of SNHG1 in glioma were also investigated using immunohistochemistry staining, Western blotting, chromatin immunoprecipitation, and RNA pulldown. Cell Counting Kit-8, transwell assays, and flow cytometry were used to investigate malignant biological behaviors. Results We have elucidated the potential molecular mechanism of long non-coding RNA SNHG1 regulating the malignant behavior of glioma cells by binding to microRNA-154-5p or miR-376b-3p. Moreover, our deep-going results showed that FOXP2 existed as a direct downstream target of both microRNA-154-5p and miR-376b-3p; FOXP2 increased promoter activities and enhanced the expression of the oncogenic gene KDM5B; and KDM5B also acts as a RNA-binding protein to maintain the stability of SNHG1. Conclusion Collectively, this study demonstrates that the SNHG1- microRNA-154-5p/miR-376b-3p- FOXP2- KDM5B feedback loop plays a pivotal role in regulating the malignant behavior of glioma cells. Graphical abstract

【 授权许可】

Unknown