MEG3 is restored by schisandrin A and represses tumor growth in choriocarcinoma cells

Abstract

Schisandrin A (SchA) has been reported as a multidrug resistance-reversing agent; however, its antitumor effects have been rarely reported. Consequently, we attempted to explore whether SchA per se possesses an antitumor property in choriocarcinoma JEG-3 and BeWo cells and its potential mechanisms. JEG-3, BeWo, and HTR-8/SVneo cells were stimulated with SchA at different concentrations (10-100 μM), and cellular viability was evaluated with Cell Counting Kit-8. After stimulation with SchA, proliferation, apoptosis, migration, and invasion were detected by bromodeoxyuridine assay, Annexin V-fluorescein isothiocyanate/ propidium iodide (Annexin V-FITC/PI) method, and a Transwell system, in JEG-3 cells transfected with short hairpin-RNA for maternally expressed 3. Western blot was performed to quantify protein. MEG3 was examined by a quantitative reverse transcription-polymerase chain reaction. MEG3 was downregulated in choriocarcinoma tissues. SchA diminished cellular viability, decreased proliferative activity, inhibited migratory and invasive behaviors, and repressed phosphorylation of regulators of phosphatidylinositol 3 kinase/protein kinase B/nuclear factor κB (PI3K/AKT/NF-κB) signaling cascade in gestational choriocarcinoma cells. MEG3 was upregulated by SchA in JEG-3 and BeWo cells. SchA exhibited little suppressive effects in JEG-3 cells lacking MEG3. Besides, the phosphorylation of transducers was evoked in MEG3-silenced JEG-3 cells despite stimulation with SchA. SchA administration repressed the growth of JEG-3 and BeWo cells by upregulating MEG3. Besides, SchA blocked PI3K/AKT/NF-κB signal cascade by elevating MEG3. K E Y W O R D S choriocarcinoma, MEG3, PI3K/AKT/NF-κB, schisandrin A

A review of current evidence about lncRNA MEG3: A tumor suppressor in multiple cancers

“…Ji and Li (2019) found that MEG3 inhibited choriocarcinoma formation by positively modulating miR-211/PI3K/AKT/AMPK signaling pathways. Similar results indicated that schisandrin A upregulated MEG3 expression and blocked the PI3K/AKT/NF-κB axis, thereby suppressing the migration and invasion of choriocarcinoma cells (Ji and Ma, 2020). Overall, these data verified that MEG3 acts as a tumor suppressor in choriocarcinoma.…”

“… Zhu et al (2018) revealed that vitamin D can induce MEG3 expression, thereby inhibiting CRC cell proliferation and migration. Ji and Ma (2020) showed that schisandrin A might suppress the growth of choriocarcinoma cells by upregulating the expression of MEG3. Gao et al (2020) explained that DNMT1 can promote the proliferation of RB cells by silencing the expression of MEG3.…”

A review: Pharmacology and pharmacokinetics of Schisandrin A

“…In choriocarcinoma cells during pregnancy, SA (10–100 μM) can reduce cell viability and proliferation activity, and inhibit migration and invasion behavior to inhibit cancer cells. In addition, SA (50 μM) also regulates the phosphorylation of the factors by inhibiting the PI3K/AKT/NF‐κB signaling cascade (Ji & Ma, 2020). This result can be achieved by increasing maternally expressed 3.…”

The Role of Long Non-Coding RNAs (lncRNAs) in Female Oriented Cancers

“…MEG3 also represses the proliferation, migration, invasion and induces apoptosis of BeWo and JEG-3 of human choriocarcinoma cells through upregulating miR-211, leading to inhibition of PI3K/AKT and AMPK pathways [ 247 ]. Moreover, a multidrug resistance-reversing agent, Schisandrin A, has been reported to repress the tumor growth in choriocarcinoma cells by upregulating MEG3 expression and downregulating PI3K/AKT/NF-κB signal cascade [ 248 ]. We summarized the detailed response of MEG3 to female-oriented cancers in Figure 8 .…”