Apelin Promotes Prostate Cancer Metastasis by Downregulating TIMP2 via Increases in miR-106a-5p Expression

Cells. 2022 Oct 19;11(20):3285. doi: 10.3390/cells11203285.

Abstract

Prostate cancer commonly affects the urinary tract of men and metastatic prostate cancer has a very low survival rate. Apelin belongs to the family of adipokines and is associated with cancer development and metastasis. However, the effects of apelin in prostate cancer metastasis is undetermined. Analysis of the database revealed a positive correlation between apelin level with the progression and metastasis of prostate cancer patients. Apelin treatment facilitates cell migration and invasion through inhibiting tissue inhibitor of metalloproteinase 2 (TIMP2) expression. The increasing miR-106a-5p synthesis via c-Src/PI3K/Akt signaling pathway is controlled in apelin-regulated TIMP2 production and cell motility. Importantly, apelin blockade inhibits prostate cancer metastasis in the orthotopic mouse model. Thus, apelin is a promising therapeutic target for curing metastatic prostate cancer.

Keywords: TIMP2; apelin; metastasis; miR-106-5p; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines* / genetics
  • Adipokines* / physiology
  • Animals
  • Apelin* / genetics
  • Apelin* / physiology
  • Cell Line, Tumor
  • Cell Movement
  • Humans
  • Male
  • Mice
  • MicroRNAs* / metabolism
  • Neoplasm Metastasis
  • Phosphatidylinositol 3-Kinases / metabolism
  • Prostatic Neoplasms* / pathology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Tissue Inhibitor of Metalloproteinase-2 / genetics

Substances

  • Adipokines
  • Apelin
  • MicroRNAs
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • TIMP2 protein, human
  • Tissue Inhibitor of Metalloproteinase-2

Grants and funding

This work was supported by the Ministry of Science and Technology, Taiwan (MOST 110-2314-B-039-012, 111-2314-B-039-051, and 110-2341-B-341-001-MY2), China Medical University Beigang Hospital (CMUBHR 108-012, 110CMURBHR-07, and CMUBHR109-007), and China Medical University hospital (DMR-110-091; DMR-111-095; DMR-111-099).