GALE Promotes the Proliferation and Migration of Glioblastoma Cells and Is Regulated by miR-let-7i-5p

Xiaopeng Sun; Hao Xue; Ye Xiong; Rui Yu; Xiao Gao; Mingyu Qian; Shaobo Wang; Huizhi Wang; Jianye Xu; Zihang Chen; Lin Deng; Gang Li

doi:10.2147/CMAR.S221585

GALE Promotes the Proliferation and Migration of Glioblastoma Cells and Is Regulated by miR-let-7i-5p

Cancer Manag Res. 2019 Dec 16:11:10539-10554. doi: 10.2147/CMAR.S221585. eCollection 2019.

Authors

Xiaopeng Sun^{1

2}, Hao Xue^{1

3}, Ye Xiong⁴, Rui Yu⁵, Xiao Gao¹, Mingyu Qian¹, Shaobo Wang¹, Huizhi Wang¹, Jianye Xu¹, Zihang Chen¹, Lin Deng^{1

3}, Gang Li^{1

3}

Affiliations

¹ Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012, People's Republic of China.
² Department of Neurosurgery, Dezhou People's Hospital, Dezhou, Shandong Province 253014, People's Republic of China.
³ Institute of Brain and Brain-Inspired Science, Shandong Provincial Key Laboratory of Brain Function Remodeling, Shandong University, Jinan, Shandong Province, People's Republic of China.
⁴ Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, People's Republic of China.
⁵ Department of Neurosurgery, The Second Hospital of Shandong University, Jinan 250033, People's Republic of China.

Abstract

Purpose: Glioma is the most common and lethal type of brain tumor. While GALE (UDP-galactose-4-epimerase) has been shown to be overexpressed in some kinds of cancers, its expression in gliomas has not been reported. MicroRNAs (miRNAs) function as tumor suppressors in many cancers, and online datasets can be used to predict whether GALE is regulated by miR-let-7i-5p. In this investigation, we explored the effect and regulatory mechanisms of GALE on glioblastoma growth via miR-let-7i-5p.

Methods: We used a Cox proportional hazards model and publicly available datasets to examine the relationship between GALE and the survival rates of glioma patients. Bioinformatics predicted the targeting of GALE by miR-let-7i-5p. The proliferation, migration, cell cycle and apoptosis of human glioblastoma cells were assessed by relevant assays. We also demonstrated the effect of GALE on glioblastoma multiforme [GBM] tumor growth using an in vivo orthotopic xenograft model.

Results: GALE was upregulated in human gliomas, especially in high-grade gliomas (e.g., GBM). An obvious decline in GALE expression was observed in human glioblastoma cell lines (U87 and U251) following treatment with a small interfering RNA (siRNA) targeting GALE or miR-let-7i-5p mimics. Knockdown of GALE or overexpression of miR-let-7i-5p (with miR-let-7i-5p mimics) inhibited U87 and U251 cell growth. miR-let-7i-5p significantly restrained the migration ability of human glioblastoma cells in vascular mimic (VM), wound healing and transwell assays, and GALE promoted glioblastoma growth in vivo.

Conclusion: Our findings confirm that GALE plays an important role in promoting the development of human glioma and that GALE can be regulated by miR-let-7i-5p to inhibit human glioblastoma growth.

Implications for cancer survivors: Our data show that cancer survivors have low GALE expression, which indicates that GALE may be a diagnostic biomarker and a promising therapeutic target in glioblastoma.

Keywords: GALE; glioblastoma; miR-let-7i-5p; migration; proliferation.

Grants and funding

This work was supported by the National Natural Science Foundation of China (nos. 81571284, 91542115, 81702468, 81874083, and 81802966), the National Natural Science Foundation of Shandong Province of China (nos. 2017CXGC1203; 2017G006012, and 2013GGE27006) and the Taishan Scholars of Shandong Province (no. ts201511093).