Solamargine inhibits gastric cancer progression by regulating the expression of lncNEAT1_2 via the MAPK signaling pathway

Abstract

Solamargine, a derivative from the steroidal solasodine in Solanum species, has exhibited anticancer activities in numerous types of cancer; however, its role in gastric cancer (GC) remains unknown. In the present study, it was demonstrated that Solamargine suppressed the viability of five gastric cancer cell lines in a dose-dependent manner and induced notable alterations in morphology. Treatment with Solamargine promoted cell apoptosis (P<0.01). Solamargine increased the expression of long noncoding RNA (lnc) p53 induced transcript and lnc nuclear paraspeckle assembly transcript 1 (NEAT1)_2 (P<0.01) in GC by reducing the phosphorylation of extracellular signal-regulated kinase (Erk)1/2 mitogen-activated protein kinase (MAPK). To gain insight into the potential mechanism, an Erk1/2 inhibitor (U0126) was applied. The results revealed that lncNEAT1_2 expression levels increased, which was consistent with the effects of Solamargine. Downregulation of lncNEAT1_2 in GC cells revealed no effect on the expression levels of total Erk1/2 and, and counteracted the effect of Solamargine. Solamargine was observed to increase the expression of lncNEAT1_2 via the Erk1/2 MAPK signaling pathway. Of note, the knockdown of lncNEAT1_2 reduced the inhibitory effect of Solamargine (P<0.05). Additionally, experiments in vivo and in primary GC cells from patients demonstrated that Solamargine significantly suppressed tumor growth (P<0.05). In vivo analysis of a xenograft mouse model further supported that Solamargine could induce the apoptosis of cancer cells in tumor tissue as observed by a terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling and H&E staining (P<0.05). Experiments in primary GC cells from patients verified the anti-tumor effect of Solamargine. In summary, the findings of the present study indicated that Solamargine inhibited the progression of GC by regulating lncNeat1_2 via the MAPK pathway.

Identification of the complex regulatory relationships related to gastric cancer from lncRNA‐miRNA‐mRNA network

“…In glioblastoma, studies have found that abnormal expression of C20orf166-AS1 leads to a decrease in survival time in patients with glioblastoma. 14,34,35 Related studies have found that the invasion and metastasis of gastric cancer cells are closely related to T A B L E 2 In the degree centrality, betweenness centrality, and closeness centrality rank the top 10 genes 33 In the C20orf166-AS1 regulatory network ( Figure 5A), there were six miRNAs and 105 mRNAs interacting with C20orf166-AS1.…”

“…Some studies have found that MAPK signaling pathway plays a key role in gastric cancer cells. 14,34,35 Related studies have found that the invasion and metastasis of gastric cancer cells are closely related to T A B L E 2 In the degree centrality, betweenness centrality, and closeness centrality rank the top 10 genes 36 Meanwhile, it is reported that cross-linked hyaluronic acid gel for preventing postoperative abdominal adhesion may inhibit MAPK/ ERK induced by epidermal growth factor (EGF), PI3K-Akt and Rac1 mediated signaling pathways have antitumor effects on gastric cancer. 37 In this study, we found that CACNA1H, FLNA, and FLNC were abnormally expressed in the MAPK signaling pathway, which provided a reference for further understanding the pathogenesis of gastric cancer.…”

The regulation and interaction of colon cancer‐associated transcript‐1 and miR7‐5p contribute to the inhibition of SP1 expression by solamargine in human nasopharyngeal carcinoma cells

“…We believed that the SM doses used in this study were reasonable and feasible which based on our and other studies (Chen, Tang, Xiao, Yang & Hann, 2017;Fu et al, 2019;Tang, Zheng, Wu, Xiao, Li & Hann, 2017). Regardless, more experiments and statistical analysis are required to further determine the critical role and correlations of CCAT1, miR7-5p and SP1, and tumor sizes in this process in mice model.…”

PolyA-modulating antisense oligonucleotides reveal opposing functions for long non-coding RNA NEAT1 isoforms in neuroblastoma

“…Dynamic changes in NEAT1 lncRNA levels are involved in tumorigenesis, where the ratio of NEAT1_1 to NEAT1_2 may be important. Various studies show NEAT1_1 primarily has a cell-proliferative role in cancer cells [18-21], whereas NEAT1_2 appearance can be associated with both tumour-suppressive and oncogenic activity [21-25]. In cancer, as well as other biological contexts, the overall transcription of NEAT1 is increased with stressors such as hypoxia, heat shock, mitochondrial stress and proteasome inhibition [26-28,18], driven by a number of upstream factors, including p53 [23,24].…”