MiR-185-3p regulates epithelial mesenchymal transition via PI3K/Akt signaling pathway by targeting cathepsin D in gastric cancer cells

Abstract

Background: Recently research reported that miR-185-3p could serve as an independent prognosis factor in gastric cancer (GC). However, the functional role and underlying mechanism of miR-185-3p in GC and epithelial-mesenchymal transition (EMT) progression remains largely elusive. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to analyze the expression of miR-185-3p and cathepsin D in patient-derived GC samples and various GC cell lines. Scratch assay and Transwell assay were used to evaluate the migration ability. The influence of miR-185-3p on the cell cycle distribution and cell apoptosis was evaluated using flow cytometry. Western blotting assay was performed to detect the expression of EMT associated proteins and the activity of PI3K/Akt signaling pathway. Furthermore, the interaction between miR-185-3p and cathepsin D was explored by dual-luciferase reporter assay.Results: Our data revealed that miR-185-3p was down-regulated, while cathepsin D was up-regulated in both patient-derived GC samples and GC cells. Apart from inducing apoptosis, overexpression of miR-185-3p also inhibited EMT process and migration of GC cells. Mechanically, we firstly verified that miR-185-3p directly targeted the cathepsin D. Furthermore, miR-185-3p exerted its function on EMT process and migration via inhibiting cathepsin D to mediated PI3K/Akt signaling pathway.Conclusions: Our findings suggested that miR-185-3p targeted cathepsin D inhibiting EMT process via PI3K/Akt signaling, which may serve as a potential prognosis factor and therapeutic target to reduce the malignancy of GCs.

RPS15A promotes gastric cancer progression via activation of the Akt/IKK‐β/NF‐κB signalling pathway

“…Cellular signalling pathways, including the Wnt/β-catenin, TGF-β, Notch, Hedgehog and NF-κB, have been demonstrated to be aberrantly activated and play vital roles in the development and progression of EMT and GC progression. 31,32 By RNA-seq and luciferase reporter assays, we identified the NF-κB pathway may be the potential effector of RPS15A. This hypothesis was subsequently confirmed by the nuclear translocation and phosphorylation of p65, increased transactivation of NF-κB reporter and up-regulation of target genes of this pathway at both mRNA and protein levels.…”

Apolipoprotein C1 regulates gastric cancer progression by inducing epithelial-mesenchymal transition via the JAK/STAT pathway

“…EMT is a phenomenon wherein epithelial cells undergo the loss of adhesion and polarity following phenotypic alterations and molecular reprogramming, acquiring enhanced migration, invasive, and metastatic capacities [38][39][40][41]. During EMT, differentiated epithelial cells exhibit alterations in markers, e.g., vimentin, N-cadherin, and E-cadherin [42][43][44]. Here, APOC1 knockdown increased E-cadherin expression and decreased N-cadherin and vimentin expression (Fig.…”

Recent progress in DNA methyltransferase inhibitors as anticancer agents

“…Hypermethylation also plays an important role in the initiation, progression, invasion, and metastasis of different types of cancer. For example, cell adhesion genes CDH1 in gastric cancer cells and CDH13 in primary non-small cell lung cancer cells are silenced due to hypermethylation, which promotes the invasion and metastasis of both types of tumor cells ( Seuk Kim et al, 2005 ; Huang et al, 2015 ). Various genes associated with DNA repair processes are also hypermethylated in tumor tissues; hypermethylation of the MLH1 gene in gastric cancer leads to abnormal DNA mismatch repair and promotes the progression of gastric cancer ( Fleisher et al, 2001 ).…”