The Role of lncRNA PVT1 and hsa-miR-30a-3p in the Development of Gastric Cancer

Objective: Aberrantly expressed lncRNAs have been detected in gastric cancer (GC). LncRNA PVT1 is involved in numerous types of human malignant tumor. In this project, we demonstrated the relationship between PVT1 and Myc and tested the function of PVT1 and hsa-miR-30a-3p in the tumorigenesis of GC.

Methods: For experimental study, RNA-Seq datasets and equivalent clinical data for 367 samples were achieved from The Cancer Genome Atlas (TCGA)-STAD datasets. The online software clusterProfiler was used to perform Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway functional enrichment. The co-expression of YY1, PVT1, and Myc genes was evaluated by determining the Pearson correlation coefficients. Potential competing endogenous RNAs of PVT1-miRNA-Myc were predicted by the Cytoscape tool and Kaplan- Meier curves were generated for YY1, PVT1, and Myc genes. For clinical study, Human GC samples were taken from 26 pairs of GC tissue (GCT) and para-tumor tissue (PT, 5 cm from the edge of the tumor) in which no patient had previously undergone preoperative adjuvant chemotherapy or radiotherapy.

Results: For experimental study, a total of 1144 differential expression genes (DEGs) were identified consisting of 731 up-regulated genes and 413 down-regulated genes. DEGs were Myc, YY1, and PVT1 and PVT1 was significantly different (adj. P=1.11E-11). The correlation coefficient between PVT1 and Myc was 0.42. A ceRNA network model suggested the hsa-miR-30a-3p was interacted between PVT1 and Myc, playing the role of information transmission. Survival analysis of these genes suggested that lncRNA PVT1 might influence the GC case survival (p=0.06). PVT1 expression was upregulated in human gastric cancer tissues and its relative PVT1 expression of PT was increased two fold compared to GCT. The expressions of PVT1 from the tumor tissues were significantly upregulated in GCT.

Conclusion: These discoveries imply that lncRNA PVT1 and hsa-miR-30a-3p has a responsibility in the GC development. Therefore, targeting PVT1 or/and hsa-miR-30a-3p as a strategy for gastric cancer should be explored.