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

Abstract

Background/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. 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.

LncRNA MEG3 inhibits the proliferation and migration abilities of colorectal cancer cells by competitively suppressing MiR-31 and reducing the binding of MiR-31 to target gene SFRP1

“…In addition, overexpression of miR-31 in these cells depletes several other antagonists of Wnt signaling that have potential miR-31 binding motifs, including SFRP1, SFRP4, and WIF-1, which are often silenced in human lung cancer [ 44 ]. Studies have shown that LncRNA MEG3 and SFRP1 can competitively bind to miR-542-3p [ 45 ]. Therefore, we inferred the competitive binding of LncRNA MEG3 and SFRP1 to miR-31 by dual luciferase assay in this experiment.…”

Targeting polycomb repressor complex 2‐mediated bivalent promoter epigenetic silencing of secreted frizzled‐related protein 1 inhibits cholangiocarcinoma progression

“…Secreted frizzled‐related protein 1 (SFRP1) has been identified as a tumour suppressor gene that is commonly downregulated in human cancers 16–18 . Over‐expression of SFRP1 can significantly inhibit the proliferation of tumour cells by negatively regulating β‐Catenin 16,19 . However, the expression of SFRP1 is highly regulated by DNA methylation 18,20,21 .…”

“… 16 , 17 , 18 Over‐expression of SFRP1 can significantly inhibit the proliferation of tumour cells by negatively regulating β‐Catenin. 16 , 19 However, the expression of SFRP1 is highly regulated by DNA methylation. 18 , 20 , 21 Generally, DNMTs regulate DNA methylation, with three common isoforms identified in humans: DNMT1, DNMT3a and DNMT3b.…”