miR218-5p regulates the proliferation of gastric cancer cells by targeting TFF1 in an Erk1/2-dependent manner

Abstract

Trefoil factor 1 (TFF1), a member of the trefoil peptide family, is not only associated with mucosal protection and restoration but is also correlated with tumorigenesis of the gastrointestinal tract. In an early study, we performed sequence analysis and identified one potential miR423-5p binding site within the 3'-untranslated region of TFF1 using microRNA target prediction tools. In the current study, we demonstrated that the coding DNA region within TFF1 is also a candidate for miR218-5p targeting. We used real-time PCR and in situ hybridization to analyze the correlation between miR218-5p and TFF1 expression in tumor lesions and paracancerous tissue in gastric cancer (GC) samples. Additionally, endogenous and exogenous TFF1 were suppressed by miR218-5p in gastric cancer cells and influenced the progression of GC in an Erk1/2-dependent manner. Targeting miR218-5p may provide a novel strategy for the treatment of GC.

miR-632 promotes gastric cancer progression by accelerating angiogenesis in a TFF1-dependent manner

“…miR-632-mimic (25 nM) and miR-632-inhibitor (50 nM) were purchased from Qiagen. The cell transfection method was described previously [28].…”

“…217184) was used for miRNA extraction from GC patient serum following the manufacturer’s protocol. miRNA first-strand cDNA synthesis and real-time PCR were performed as previously described [28]. miR-632 and control primers were purchased from Qiagen.…”

“…According to a computer-based set of predictions, target sequences within the TFF gene cluster demonstrate that multiple miRNAs can potentially bind the 3′-untranslated region and DNA coding sequence [26]. We previously showed that miR-423-5p and miR-218-5p regulate GC proliferation and invasion by targeting TFF1, respectively [27, 28].…”

Trefoil factors: Gastrointestinal-specific proteins associated with gastric cancer

“…The function of miR-423-5p on proliferation induction and invasion inhibition may result in the decrease of TFF1 and the increase of cyclin D1, cyclin D3, and β-catenin expression which can promote the progression of GCs [26]. A recent study has demonstrated that miR218-5p restrains TFF1 in an extracellular signal-regulated kinase 1/2 (Erk1/2)-dependent manner, then motivates the proliferation of human GC cells [128]. Targeting miR218-5p may provide a novel tactic for the treatment of GC.…”

Cloning of a novel lectin from Artocarpus lingnanensis that induces apoptosis in human B-lymphoma cells

“…ERK1/2 activation is associated with cell cycle progression, differentiation, protein translation and cell death. JNK and p38 MAPK pathways modulate cellular senescence and oncogenic transformation and play a key role in the proliferation, differentiation, survival and death of cancer cells [31,32]. JNK and p38 can have antagonist effects.…”