MicroRNA-140-5p inhibits cell proliferation, migration and promotes cell apoptosis in gastric cancer through the negative regulation of THY1-mediated Notch signaling

Abstract

Studies have highlighted the importance of microRNAs (miRs) in the development of various cancers, including gastric cancer (GC), a commonly occurring malignancy, accompanied by high recurrence and metastasis rate. The aim of the current study was to investigate the role of miR-140-5p in GC. Microarray expression profiles were initially employed to screen the differentially expressed gene related to GC, and the miR regulating the gene was predicted accordingly. The data obtained indicated that thymus cell antigen 1 (THY1) was differentially expressed in GC and confirmed to be a target gene of miR-140-5p. Poorly expressed miR-140-5p and highly expressed THY1 were observed in the GC tissues. SGC-7901 cells were treated with miR-140-5p mimic/inhibitor, siRNA against THY1 and siRNA against Notch1 in order to determine their regulatory roles in GC cell activities. The relationship of miR-140-5p, THY1 and the Notch signaling pathway was subsequently identified. Moreover, cell proliferation, migration, invasion and apoptosis were determined using 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethonyphenol)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), wound-healing, transwell assay and flow cytometry, respectively. The overexpression of miR-140-5p and silencing of THY1 resulted in a diminished expression of the Notch signaling pathway-related proteins, as well as inhibited proliferation, migration and invasion of GC cells, enhanced expression of pro-apoptotic proteins in addition to elevated apoptosis rate. Taken together, the present study suggests that miR-140-5p directly targets and negatively regulates THY1 expression and inhibits activation of the Notch signaling pathway, whereby the up-regulation of miR-140-5p inhibits development of GC, highlighting the promise of miR-140-5p as a potential target for GC treatment.

<p>Long Non-Coding RNA TMPO-AS1 Promotes Cell Migration and Invasion by Sponging miR-140-5p and Inducing SOX4-Mediated EMT in Gastric Cancer</p>

“…One of the popular action mechanisms of lncRNAs is to serve as a competing endogenous RNA (ceRNA) to regulate the expression and function of target genes by binding and sequestering with miRNAs. 13 Among many miRNAs, miR-140-5p was selected as a candidate for further analysis since several publications have reported its tumor-suppressive role in GC, [14][15][16] and in this study, we confirmed that TMPO-AS1 negatively regulated miR-140-5p expression in GC cells, and the oncogenic effects of TMPO-AS1 overexpression on GC cells were partially reversed by miR-140-5p restoration. MiRNAs exert their functions by negative regulation of their target genes, 17 and this study further showed that miR-140-5p directly targets SOX4, a master mediator of EMT in GC cells.…”

MicroRNA-140-5p inhibits salivary adenoid cystic carcinoma progression and metastasis via targeting survivin

“…MiR-140-5p was down-regulated in hypopharyngeal squamous cell carcinoma (HSCC) tissues and cell lines and restoration of miR-140-5p in HSCC cells repressed tumor cell invasion and migration via targeting ADAM10/Notch1 axis [18]. Fang et al, showed that down-regulated miR-140-5p expression was detected in the cancerous gastric clinical samples and was correlated with shorter overall survival of gastric cancer patients; mechanistically, miR-140-5p exerted its tumor-suppressive effects on gastric cancer via targeting YES1 and THY/Notch signaling [16, 19]. A recent study by Liu et al [13], showed that miR-140-5p was down-regulated in Wilms’ tumor and suppressed tumor progression via modulating TGFBRI/SMAD2/3 and IGF-1R/AKT signaling pathways.…”

“…In addition, a further study using miRNA array screening identified the down-regulation of miR-140-5p in SACC [11]. The tumor-suppressive role of miR-140-5p has been elucidated in various types of malignancies [12–16]. However, the involvement of miR-140-5p in SACC progression and metastasis has not been elucidated yet.…”

Bioinformatics Analysis and Identification of Potential Biomarkers in Gastric Cancer

“…Furthermore, THY1 has been proven to be a target gene of miR-140-5p (65). Wu et al has indicated that miR-140-5p can inhibit the development of gastric cancer by inhibiting the expression of THY1 and inactivating Notch signaling pathway (65). According to the above studies, THY1 can be used as a target for the treatment of GC, and it is worth further exploring its value in early detection.…”