Sulforaphane inhibits gastric cancer progression by regulating the YY1/PSMB8-AS1/miR-888-5p/SLC4A7 axis

Sulforaphane (SFN) plays a vital role in many types of cancer as a natural extract from plants. However, whether SFN can inhibit gastric carcinogenesis by regulating the lncRNA-miRNA-mRNA axis is unclear. In the current work, the significantly differentially expressed lncRNA PSMB8AS1 was obtained by performing high-throughput sequencing of gastric cancer cells treated with SFN. The qRT-PCR assay results confirmed the inhibitory effect of SFN on PSM8AS1. Subsequently, using gastric cancer data from TCGA and 11 pairs of clinical samples from gastric and paracancerous tissues, we found that PSMB8-AS1 was upregulated in gastric cancer, and high expression of PSMB8-AS1 was associated with low survival of patients with gastric cancer. MTT, cell colony formation, scratch healing, flow cytometry, and qRT-PCR assays showed that the knockdown of PSMB8-AS1 significantly reduced the proliferation and migration of gastric cancer cells as well as promoted apoptosis. Dual luciferase reporter gene and RNA immunoprecipitation (RIP) assay confirmed that PSMB8-AS1 can function as the molecular sponge for miR-888-5p. Meanwhile, bioinformatics analysis and dual-luciferase reporter gene assay showed that miR-888-5p regulates SLC4A7. Overexpression of miR-888-5p or knockdown of SLC4A7 reduced the proliferation and migration of gastric cancer cells. In addition, rescue experiments confirmed that the inhibitory effects of the knockdown of PSMB8-AS1 or the knockdown of SLC4A7 on the proliferation and migration of gastric cancer cells could be reversed by miR-888-5p inhibitor treatment. Subcutaneous tumor formation experiments in nude mice demonstrated that the tumor volume of nude mice transplanted with PSMB8-AS1-knockdown gastric cancer cells was significantly reduced compared with that of the control group. Transcription factors can usually bind to the promoter regions of lncRNAs and regulate the transcription of lncRNAs. We demonstrated through website prediction and experiments that SFN can inhibit the level of PSMB8-AS1 by regulating the transcription factor YY1. These results suggest that SFN inhibits gastric cancer growth through the YY1/PSMB8-AS1/miR-888-5p/SLC4A7 axis. Therefore, SFN might be a promising therapeutical agent for GC prevention and therapy.