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

摘要

OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: VIM-AS1/miR-105-5p/WEE1 signaling may be a promising target for glioma treatment.