Protective role of astragaloside IV in gastric cancer through regulation of microRNA-195-5p-mediated PD-L1

Abstract

Aim

Astragaloside IV (AS-IV) was reported to exert anti-cancer function in many cancers, but its actions in gastric cancer (GC) remain unclear. In the present study, we tried to elaborate the underlying mechanism by which AS-IV regulated the epithelial-mesenchymal transition (EMT) and angiogenesis of GC cells.

Methods

The expressions of hsa-miR-15b-5p, hsa-miR-15a-5p, hsa-miR-195-5p, hsa-miR-424-5p and hsa-miR-497-5p in GC tissues and adjacent normal tissues were predicted by TCGA database. SGC7901 or MGC803 cells were treated with AS-IV, or transfected with miR-195-5p inhibitor/mimic or pcDNA3.1-PD-L1 followed by detection of cell proliferation, EMT and angiogenesis. The target relation between miR-195-5p and PD-L1 was confirmed by dual luciferase reporter gene assay.

Results

Elevated hsa-miR-15b-5p, hsa-miR-15a-5p and hsa-miR-424-5p expressions were found in GC tissues, while decreased hsa-miR-195-5p and hsa-miR-497-5p expressions were observed in GC tissues. AS-IV inhibits EMT and angiogenesis in GC. PD-L1 was a potential target of miR-195-5p. Down-regulation of miR-195-5p or elevated PD-L1 expression reverses the inhibitory effect of AS-IV on EMT and angiogenesis of GC cells.

Conclusion

The present study demonstrated that AS-IV inhibited EMT and angiogenesis in GC through upregulation of miR-195-5p, highlighting the potential therapeutic effect of AS-IV on GC via miR-195-5p-regulated PD-L1.

Keywords:

• Gastric cancer
• astragaloside IV
• microRNA-195-5p
• PD-L1
• Epithelial-mesenchymal transition
• angiogenesis

Acknowledgement

Thanks for all the contributors.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was funded by the grant from Hunan Provincial Science and Technology Planning Project [Grant No. 2016SK2008].