miR-573 suppresses pancreatic cancer cell proliferation, migration, and invasion through targeting TSPAN1

Strahlenther Onkol. 2021 May;197(5):438-448. doi: 10.1007/s00066-020-01728-3. Epub 2020 Dec 15.

Abstract

Purpose: To explore whether miR-573 can suppress pancreatic cancer cell proliferation, migration, and invasion by targeting TSPAN1.

Methods: The expression of miR-573 and TSPAN1 in pancreatic cancer tissues and cells lines was analyzed using RT-qPCR. The human pancreatic cancer cell line PANC‑1 was transfected with miR-573 mimic, pcDNA3.1-TSPAN1, or genOFFTM st-h-TSPAN1. The effects of miR-573 and TSPAN1 on cell proliferation, colony formation, migration, and invasion were analyzed by CCK‑8, colony formation, transwell migration, and invasion assay, respectively. Target genes of miR-573 were screened using bioinformatics tools and confirmed by dual-luciferase reporter assay and real-time PCR. The effects of miR-573 in vivo were observed using tumor xenografts.

Results: We found that miR-573 is downregulated and TSPAN1 is upregulated in pancreatic cancer tissues and cells lines. Function assays demonstrated that overexpression of miR-573 inhibited cell proliferation, colony formation, migration, and invasion of pancreatic cancer cells, as well as suppressing tumor growth in vivo. Target genes of miR-573 were predicted using bioinformatics tools and confirmed by dual-luciferase reporter assay and RT-qPCR or western blotting. Downregulation of TSPAN1 also inhibited cell proliferation, colony formation, migration, and invasion of pancreatic cancer cells. Furthermore, overexpression of TSPAN1 attenuated miR-573-induced inhibition of pancreatic cancer cell proliferation and migration.

Conclusion: Our findings indicated that miR-573 suppresses pancreatic cancer cell proliferation, migration, and invasion through targeting TSPAN1. TSPAN1 targeted by miR-573 might be a potential therapeutic target for clinical treatment of pancreatic cancer.

Keywords: Invasion; Migration; Pancreatic cancer; Proliferation; TSPAN1; miR-573.

MeSH terms

  • Animals
  • Cell Division
  • Cell Line, Tumor
  • Cell Movement
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic / genetics
  • Genes, Reporter
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • MicroRNAs / therapeutic use
  • Neoplasm Invasiveness
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Pancreatic Neoplasms / pathology*
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / physiology*
  • Random Allocation
  • Real-Time Polymerase Chain Reaction
  • Specific Pathogen-Free Organisms
  • Tetraspanins / antagonists & inhibitors*
  • Tetraspanins / biosynthesis
  • Tetraspanins / genetics
  • Tumor Stem Cell Assay
  • Xenograft Model Antitumor Assays

Substances

  • MIRN573 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm
  • TSPAN1 protein, human
  • Tetraspanins