lncRNA HOXC-AS1 promotes gastric cancer via binding eIF4AIII by activating Wnt/β-catenin signaling

Background: Long non-coding RNAs (lncRNAs) function as oncogenes or tumor suppressor genes in several cancers. The present study aimed to determine the functions of lncRNA HOXC-AS1 in gastric cancer (GC) in vitro.

Methods: A quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to measure the expression of lncRNA HOXC-AS1 in GC cell lines and normal cells. After silencing HOXC-AS1 in GC cells, a cell counting kit-8 assay monitored the viability of the cells. qRT-PCR and western blot documented the EMT key genes in response to HOXC-AS1 change. qRT-PCR detected mRNA expression for eIF4AIII in GC and normal cell lines and cell viability was measured after an increase and decrease of eIF4AIII. RNA pull-down and qRT-PCR confirmed the binding in between. Apoptosis was compared by flow cytometry. The interplay between the two genes was surveyed by introduction of the sh-HOXC-AS1 and sh-eIF4AIII and by assessing cell viability, EMT and Wnt/β-catenin signaling.

Results: lncRNA HOXC-AS1 expression is up-regulated in GC cells and a decrease of lncRNA HOXC-AS1 inhibited cell viability. Binding was validated by RNA pull-down. Additionally, inhibition of eIF4AIII induced an increase of lncRNA HOXC-AS1, thus promoting cell proliferation and the EMT process but deterring apoptosis of gastric cancer cells. Wnt/β-catenin signaling was impeded by HOXC-AS1 inhibition but restored by suppression of eIF4AIII.

Conclusions: HOXC-AS1 may promote the proliferation and the EMT process and inhibit apoptosis by binding eIF4AIII via Wnt/β-catenin signaling, which indicates that HOXC-AS1/eIF4AIII might be an axis that could be further used as a biomarker to help with the diagnosis of GC.