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

Oncol Rep. 2021 May;45(5):59. doi: 10.3892/or.2021.8010. Epub 2021 Mar 24.

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 proliferation, 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 correlations 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 positively 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 modulates tumorigenesis in PC, which may be associated with the Wnt/β‑catenin signaling pathway.

Keywords: long non‑coding RNA GATA3‑antisense RNA 1; microRNA‑30b‑5p; testis‑expressed protein 10; tumorigenesis; pancreatic cancer.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Animals
  • Apoptosis / genetics
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Mice
  • MicroRNAs / metabolism*
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Pancreas / pathology
  • Pancreas / surgery
  • Pancreatectomy
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / surgery
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Up-Regulation
  • Wnt Signaling Pathway / genetics
  • Xenograft Model Antitumor Assays

Substances

  • MIRN30b microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Long Noncoding
  • TEX10 protein, human