MiR-337 suppresses pancreatic cancer development via STAT3/Wnt/β-catenin axis

Anticancer Drugs. 2021 Aug 1;32(7):681-692. doi: 10.1097/CAD.0000000000001044.

Abstract

MiRNA is an important regulator of tumorigenesis and tumor progression. MiR-337 expression was increased in pancreatic cancer tissues and it was associated with patients' survival. This study aimed to explore the influence and the potential working mechanism of miR-337 on the malignant behaviors of pancreatic cancer cells. MiR-337 expression was detected by qRT-PCR. The expression levels of STAT3, epithelial-mesenchymal transition-related genes and Wnt/β-Catenin pathway genes were evaluated by qRT-PCR and western blot. Cell counting kit -8 and colony formation assays were conducted to examine the proliferation of AsPC-1 and SW1990 cells. Wound healing and transwell assays were performed to determine the migration and invasion of AsPC-1 and SW1990 cells. The predicted target gene of miR-337 was verified by luciferase reporter assay. The expression of miR-337 was decreased and STAT3 expression was increased in pancreatic cancer tissues as well as tumor cells. Overexpression of miR-337 suppressed proliferation, invasion and migration of AsPC-1 and SW1990 cells. MiR-337 targeted 3'UTR of STAT3 and inhibited STAT3 expression. In addition, exogenous STAT3 partially restored the inhibitory role of miR-337 on proliferation, invasion and migration of AsPC-1 and SW1990 cells. Moreover, miR-337 impeded the expression of Wnt/β-catenin pathway-related genes. Through the saving experiment, we found that the inhibitory effect of miR-337 on AsPC-1 and SW1990 cells was abolished by the addition of LiCl. These outcomes expounded that miR-337 inactivated the Wnt/β-catenin pathway to suppress the malignant behaviors of pancreatic cancer cells through targeting STAT3. This study may provide a novel biomarker for diagnosis and a new therapeutic target for pancreatic cancer treatment.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition / physiology*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / biosynthesis*
  • Pancreatic Neoplasms / pathology*
  • STAT3 Transcription Factor / metabolism*
  • Wnt Signaling Pathway / physiology*
  • beta Catenin / metabolism*

Substances

  • MicroRNAs
  • Mirn337 microRNA, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • beta Catenin