Knockdown of long non-coding RNA VIM-AS1 inhibits glioma cell proliferation and migration, and increases the cell apoptosis via modulation of WEE1 targeted by miR-105-5p.

Abstract

Glioma including glioblastoma is the main type of primary brain tumors worldwide. LncRNAs have participated in glioma formation. This study aims to investigate the underlying mechanism for VIM-AS1/miR-105-5p/WEE1 signaling in glioma. The clinical tumors and adjacent tissues were collected from 24 patients with glioma in the Shang Luo Central Hospital. Then, the clinical samples were subjected to hematoxylin-eosin staining (H&E). VIM-AS1, miR-105-5p, and WEE1 levels were measured using real-time PCR. The protein levels of WEE1, Cyclin A1, PCNA, N-cadherin, Vimentin, and Bcl-2, E-cadherin, and Bax were analyzed using Western blot. The overall survival of glioma patients was evaluated using the Kaplan-Meier analysis. The interaction between VIM-AS1 and miR-105-5p was determined using RIP assay and Dual-Luciferase reporter assay, and the binding between miR-105-5p and WEE1 was also detected by Dual-Luciferase reporter assay. Cell proliferation, colony formation, cell cycle, apoptosis, and migration were confirmed using CCK-8, colony formation assay, flow cytometry, and transwell assay, respectively. VIM-AS1 was elevated in cancer tissues, and high level of VIM-AS1 was positively correlated with poor overall survival. Then, VIM-AS1 could bind to and downregulate miR-105-5p. Furthermore, the knockdown of VIM-AS1 significantly suppressed tumor growth in vivo. The knockdown of VIM-AS1/overexpression of miR-105-5p inhibited glioma cell growth, colony formation, and migration, and enhanced the cell apoptosis by inhibiting expression of Cyclin A1, PCNA, Vimentin, N-cadherin, and Bcl-2, and by increasing the expression of Bax and E-cadherin. Interestingly, the overexpression of VIM-AS1 reversed the tumor-suppressing role of miR-105-5p in glioma cells. Besides, the expression of WEE1 was synergistically regulated by VIM-AS1 and miR-105-5p. Consequently, VIM-AS1 promoted glioma progression via upregulating WEE1 or downregulating miR-105-5p. VIM-AS1/miR-105-5p/WEE1 signaling may be a promising target for glioma treatment.