Marsdenia tenacissima extract prevents the malignant progression of glioma through upregulating lncRNA MEG3 and SFRP1-dependent inhibition of Wnt/β-catenin pathway

通关藤提取物通过上调lncRNA MEG3和SFRP1依赖的Wnt /β-catenin通路抑制来阻止胶质瘤的恶性进展

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作者:Lei Chen, Xin Gong, Mengyi Huang

Aim

Recent studies have highlighted the tumor-suppressive effect of Marsdenia tenacissima extract (MTE) on human cancers. This research unveils the potential impact of MTE on glioma and ascertains the relevant molecular mechanisms.

Conclusions

MTE suppresses glioma via the lncMEG3/miR-542-3p/SFRP1/Wnt/β-catenin axis. These findings contribute to a theoretical basis for the use of MTE for glioma patients.

Methods

Glioma cells were treated with MTE, with normal human astrocytes (NHAs) as controls. A battery of function experiments, including the CCK-8 viability test, colony formation assay, scratch migration assay, and Transwell invasion assay, was executed to address the responses of glioma cells to MTE treatment and gain or loss of function of lncMEG3, miR-542-3p, and SFRP1. FISH, RIP, and dual-luciferase reporter assays were adopted for assessing gene interactions. U251-GFP-Luc cells were delivered into nude mice through intracranial injection to develop an orthotopic glioma model for in vivo validation.

Results

200 mg/mL MTE could suppress the proliferating, migrating, and invading properties of glioma cells but not affect those of NHAs. MTE treatment enhanced the expression of lncMEG3, which competes with SFRP1 for binding miR-542-3p. SFRP1 could inactivate the Wnt/β-catenin pathway. Animal experimentation substantiated the antitumor activity and mechanism of MTE in nude mice. Conclusions: MTE suppresses glioma via the lncMEG3/miR-542-3p/SFRP1/Wnt/β-catenin axis. These findings contribute to a theoretical basis for the use of MTE for glioma patients.

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