LncRNA FOXD3-AS1 Contributes to Glioblastoma Progression Via Sponging miR-3918 to Upregulate CCND1

• Published in: Turkish neurosurgery Vol. 34; no. 2; p. 224
• Main Authors: Huang, Conggang, Shao, Ting, Duan, Faliang, Li, Ruixue, Luo, Ming, Huang, Qiaochun, Wang, Yuan, Luo, Zhihua
• Format: Journal Article
• Language: English
• Published: Turkey 01.01.2024
• Subjects: Animals; Cell Line, Tumor; Cell Proliferation - genetics; Cyclin D1 - genetics; Cyclin D1 - metabolism; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Gene Expression Regulation, Neoplastic; Glioblastoma - genetics; Humans; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism
• ISSN: 1019-5149; 2651-5032
• DOI: 10.5137/1019-5149.JTN.38366-22.2

To elucidate the pro-tumorigenic role of IncRNA FOXD3-AS1 in glioblastoma. The expression of miR-3918, FOXD3-AS1, and CCND1 was measured in glioblastoma cells and tissues using reverse transcriptase quantitative PCR (RT-qPCR). The effect of FOXD3-AS1 silencing on the proliferation of glioblastoma cells was assessed in vitro using CCK-8 and colony formation assays and in vivo using xenograft mouse models. Additionally, the expression levels of the apoptosis-related proteins, Bcl-2 and Bax, were assessed using western blotting. Bioinformatic analysis and luciferase reporter assays assisted by RNA immunoprecipitation (RIP) and RNA pull-down experiments were conducted to validate the interactions among FOXD3-AS1, CCND1, and miR-3918. FOXD3-AS1 and CCND1 were highly expressed in glioblastoma tissues and cells, whereas miR-3918 was poorly expressed. The expressions of FOXD3-AS1 and CCND1 were inversely associated with miR-3918 levels in glioblastoma tissues. FOXD3-AS1 silencing weakened the proliferative capacity and accelerated apoptosis of glioblastoma cells in vitro and hampered tumor growth in vivo. Mechanical investigations showed that FOXD3-AS1 knockdown increased miR-3918 expression and inhibited glioblastoma cell growth. Meanwhile, the miR-3918 inhibitor restored CCND1 expression and induced the opposite outcome. FOXD3-AS1 facilitates the CCND1-driven progression of glioblastoma by serving as a competing endogenous RNA (ceRNA) for miR-3918. This suggests that FOXD3-AS1 may be a potential therapeutic target for the management of glioblastoma development.