Long noncoding RNA HCG18 up-regulates the expression of WIPF1 and YAP/TAZ by inhibiting miR-141-3p in gastric cancer

Bladder Cancer

Cancer Med. 2020 Jul 29. doi: 10.1002/cam4.3288. Online ahead of print.


BACKGROUND: Accumulating works show that lncRNAs play critical roles in the development of gastric cancer (GC). LncRNA HLA complex group 18 (HCG18) was implicated in the progression of bladder cancer and glioma, but its role in GC is unknown.

METHODS: RT-PCR was used to detect HCG18 and miR-141-3p expression in GC specimen. GC cell lines (AGS and MKN-28) were exploited as cell model. The biological effect of HCG18 on cancer cells was probed by CCK-8, colony formation, flow cytometry, Transwell and wound-healing experiments in vitro, and subcutaneous xenotransplanted tumor model and tail vein injection model in vivo. Interaction between HCG18 and miR-141-3p was determined by bioinformatics analysis, RT-PCR, and luciferase reporter experiments. Downstream gene expression of miR-141-3p, including Wiskott-Aldrich syndrome protein interacting protein family member 1 (WIPF1), Yes associated protein 1 (YAP), and tafazzin (TAZ) were detected using Western blot.

RESULTS: HCG18 was markedly up-regulated in GC specimens, while miR-141-3p was markedly down-regulated. Down-regulation of HCG18 inhibited viability, migration, and invasion of GC cells, while miR-141-3p transfection led to opposite effect. HCG18 could down-regulate miR-141-3p through adsorbing it, and a negative association between HCG18 and miR-141-3p was found in GC specimens. HCG18 promoted WIPF1, YAP and TAZ expression, nonetheless, such influence was reversed by co-transfecting with miR-141-3p.

CONCLUSION: HCG18 was aberrantly up-regulated in GC tissues, and it indirectly regulated the activity of Hippo signaling through counteracting miR-141-3p expression.