Arsenic sulfide induces miR-4665-3p to inhibit gastric cancer cell invasion and migration

Abstract

Purpose

Gastric carcinogenesis is a multistep process and is the second-highest cause of cancer death worldwide with a high incidence of invasion and metastasis. MicroRNAs (miRNAs) engage in complex interactions with the machinery that controls the transcriptome and concurrently target multiple mRNAs. Recent evidence has shown that miRNAs are involved in the cancer progression, including promoting cell-cycle, conferring resistance to apoptosis, and enhancing invasiveness and metastasis. Here, we aim to elucidate the roles of miRNAs, especially microRNA-4665-3p (miR-4665-3p), in the inhibitory effect of arsenic sulfide in gastric cancer (GC).

Methods

The arsenic sulfide-induced miRNA expression alterations in AGS cells was determined by miRNA microarray. RT-PCR was used to further verify the arsenic sulfide-regulated miRNAs in GC tissues. The inhibition of miR-4665-3p on the migration and invasion of GC cells were determined by wound healing assay and transwell assay. Western blot analysis was used to detect the expression of EMT related proteins and the putative target of miR-4665-3p.

Results

The miR-4665-3p was up-regulated by arsenic sulfide and showed inhibition upon the migration and invasion of GC cells. MiRBase and Western blotting indicated that miR-4665-3p directly down-regulated the oncoprotein GSE1. Morphological observation also indicated that the up-regulation of miR-4665-3p inhibits the EMT in GC cells.

Conclusion

Our data demonstrates that the increased expression of miR-4665-3p induced by arsenic sulfide suppresses the cell invasion, metastasis and EMT of GC cells, and has the potential to be a novel therapeutic target in GC.

Keywords:

• arsenic sulfide
• miR-4665-3p
• gastric cancer
• invasion
• migration

Acknowledgments

This work was supported by the National Science Foundation of China (81874353 and 81274142), and the Science and Technology Commission of Shanghai Municipality (17401931300 and 11ZR1423400).

Disclosure

The authors report no conflicts of interest in this work.

Supplementary material

Figure S1 The alteration of miRNAs after treated with As₄S₄ in MGC803 and HCT116.

Notes: (A) miR-135b-5p, (B) miR-4665-3p, (C) miR-4739, (D) miR-6124. MiR-135b-5p, miR-4665-3p and miR-4739 are up-regulated while miR-6124 is down-regulated after incubation with As₄S₄ in both MGC803 cells and HCT116 cells. **P<0.01, ***P<0.001.