Turkish Neurosurgery 2024 , Vol 34 , Num 2
LncRNA FOXD3-AS1 Contributes to Glioblastoma Progression Via Sponging miR-3918 to Upregulate CCND1
Conggang HUANG1,Ting SHAO1,Faliang DUAN1,Ruixue LI2,Ming LUO1,Qiaochun HUANG1,Yuan WANG1,Zhihua LUO1
1Wuhan No.1 Hospital, Department of Neurosurgery, Wuhan 430022, Hubei, China
2Wuhan No.6 Hospital, Intensive Care Unit, Wuhan 430014, Hubei, China
DOI : 10.5137/1019-5149.JTN.38366-22.2 AIM: To elucidate the pro-tumorigenic role of IncRNA FOXD3-AS1 in glioblastoma.

MATERIAL and METHODS: 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.

RESULTS: 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.

CONCLUSION: 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. Keywords : Glioblastoma, Competing endogenous RNA (ceRNA), lncRNA FOXD3-AS1, Proliferation

Corresponding author : Zhihua LUO, zhihualuo5@163.com