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

• Main Authors: Han Li, Yixue Xue, Jun Ma, Lianqi Shao, Di Wang, Jian Zheng, Xiaobai Liu, Chunqing Yang, Qianru He, Xuelei Ruan, Zhen Li, Yunhui Liu
• Format: Article
• Language: English
• Published: BMC 2019-02-01
• Series: Journal of Experimental & Clinical Cancer Research
• Subjects: Long non-coding RNA; microRNA; Transcription factor; Glioma; Oncogenes
• Online Access: http://link.springer.com/article/10.1186/s13046-019-1063-9

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