PMEPA1 Stimulates the Proliferation, Colony Formation of Pancreatic Cancer Cells via the MAPK Signaling Pathway

Am J Med Sci. 2021 Sep;362(3):291-296. doi: 10.1016/j.amjms.2021.04.002. Epub 2021 Apr 13.

Abstract

Background: Prostate transmembrane protein androgen-induced 1 (PMEPA1) is reportedly highly expressed in pancreatic cancer (PC). However, its biological role and associated mechanisms have not been addressed in PC progression.

Methods: PMEPA1 mRNA expression and survival outcome of PC patients were evaluated via the GEPIA website. Lentiviral-mediated shRNA knockdown and ectopic expression of PMEPA1 were implemented in the pancreatic cancer cell line PANC1 cells. CCK-8 and colony formation assays were carried out to assess the biological function of PMEPA1 in PANC1 proliferation and viability. Dual-luciferase reporter assays and RT-qPCR were used to assess the interactive relationship between PMEPA1 and the MAPK signaling pathway.

Results: By analyzing the data from GEPIA, we found that PMEPA1 mRNA expression is overexpressed in PC tissues compared with matched nontumor tissues. PMEPA1-high PC patients are predicted to have a worse prognosis than PMEPA1-low PC patients. We found that PMEPA1 shRNA suppressed PANC1 proliferation and colony formation capacity, while enforced expression of PMEPA1 yielded the opposite results. Mechanical investigations showed that PMEPA1 exerts its tumor-promoting function in pancreatic cancer via activation of the MAPK signaling pathway.

Conclusion: PMEPA1 promotes the progression of PC at least partially by activating the MAPK signaling pathway; thus, the PMEPA1/MAPK axis may be a potential therapeutic target in pancreatic cancer.

Keywords: Colony formation; PMEPA1; Pancreatic cancer; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Cell Line, Tumor
  • Cell Proliferation / physiology*
  • HEK293 Cells
  • Humans
  • MAP Kinase Signaling System / physiology*
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • Neoplastic Stem Cells / metabolism*
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*

Substances

  • Biomarkers, Tumor
  • Membrane Proteins
  • PMEPA1 protein, human