HOTAIR contributes to the carcinogenesis of gastric cancer via modulating cellular and exosomal miRNAs level

Gastric cancer (GC) is one of the most leading malignancies. Long noncoding RNA is related to GC. In this study, 11 miRNAs in the exosomes and six lncRNAs in the tissues was examined by qRT-PCR. Correlation analysis was used to analyze the relationship between miRNAs in exosome and lncRNAs in the tissues. Four miRNAs level in GC tissues were examined by qRT-PCR. MTT was used to determine cell viability. Flow cytometry was used to quantify the apoptotic cells. Transwell assay was used to examine the migration and invasion capacity. Dual-luciferase assay was used to examine the interaction between HOTAIR and miR-30a or -b. Capillary formation was used to determine the capillary formation capacity. Weak negative correlations were found between HOTAIR and miR-30a or -b in GC tissue samples. Interestingly, strong negative correlations were identified between the HOTAIR level in GC tissue samples and the miR-30a or -b levels in plasma exosomes. HOTAIR knockdown GC cells exhibited decreased migration, invasion, proliferation, and upregulated apoptosis, which released more miR-30a and -b into the exosomes. KRAS was upregulated when co-cultured with exosomes from HOTAIR overexpressed cells, and promoted GC cells proliferation, migration, and invasion. Meanwhile, HUVEC cells expressed increased VEGF-A and formatted more capillaries. Subsequently, we identified a 10mer target site of miR-30a or -b in HOTAIR sequence, and the overexpression of HOTAIR induced the degradation of miR-30a or -b, indicating a ceRNA role of HOTAIR. We report the negative correlation between the plasma miRNAs level and GC tissue HOTAIR expression for the first time and unveiled the ceRNA role of HOTAIR in GC. HOTAIR functions as an onco-lncRNA regulating the level of miR-30a and -b in both GC cells and exosomes. These findings may give insight into understanding the mechanism of GC pathogenesis and provide new biomarkers for clinical diagnosis.