LncRNA GATA3-AS1-miR-30b-5p-Tex10 axis modulates tumorigenesis in pancreatic cancer

Abstract

Long noncoding RNAs (lncRNAs) have been widely recognized to play an important role in a variety of diseases. Abnormal regulation of lncRNA GATA3-antisense RNA 1 (AS1) occurs in several cancers, but whether it is involved in the progression of pancreatic cancer (PC) remains unknown. The present study aimed to investigate the biological effects of GATA3-AS1 in PC and to explore the underlying molecular mechanisms. Upregulation of GATA3-AS1 was revealed in PC tissues and cell lines. Knockdown of GATA3-AS1 in PANC-1 or AsPC-1 cells markedly reduced cell viability, cell prolif- eration, and cell invasion abilities, while cell apoptosis was increased. In addition, GATA3-AS1 knockdown suppressed the stemness of PANC-1 and AsPC-1 cells by decreasing the spheroid formation ability. A tumor xenograft in vivo assay demonstrated that GATA3-AS1 knockdown inhibited tumorigenicity of AsPC-1 cells. Furthermore, the microRNA (miR)-30b-5p downregulation and GATA3-AS1 upregulation were revealed in PC tissues and cell lines. Negative correla- tions were present between GATA3-AS1 and miR-30b-5p and between miR-30b-5p and testis-expressed protein 10 (Tex10) in the PC tissues, while GATA3-AS1 and Tex10 were posi- tively correlated. GATA3-AS1 was then revealed to act as a competing endogenous RNA (ceRNA) for miR-30b-5p in regulating Tex10 expression. Moreover, the miR-30b-5p-Tex10 axis was confirmed to be involved in the regulation of biological effects of GATA3-AS1, including cell viability, cell proliferation, cell invasion, cell apoptosis, and cell stemness, as well as Wnt1/β-catenin signaling. Collectively, these data indicated that the GATA3-AS1-miR-30b-5p-Tex10 axis modu- lates tumorigenesis in PC, which may be associated with the Wnt/β-catenin signaling pathway.