GRSF1 promotes tumorigenesis and EMT-mediated metastasis through PI3K/AKT pathway in gastric cancer

Biochem Biophys Res Commun. 2021 May 28:555:61-66. doi: 10.1016/j.bbrc.2021.03.121. Epub 2021 Apr 1.

Abstract

It is vital to identify effective therapeutic targets and explore the underlying mechanisms to curb the progression of Gastric cancer (GC) and improve the prognosis of GC patients. Guanine-rich RNA sequence binding factor 1 (GRSF1) is a member of the RNA-binding protein family. The present study showed that GRSF1 knockdown suppressed GC cells proliferation, migration and invasion in vitro, while GRSF1 overexpression enhanced the proliferation, migration and invasion of GC cells. Meanwhile, knockdown of GRSF1 inhibited tumor growth and tumor metastasis in vivo. Furthermore, we demonstrated that GRSF1 induced epithelial-mesenchymal transition (EMT) and activated PI3K/AKT pathway in vitro and in vivo through gain and loss of function. In conclusion, we demonstrated that GRSF1 promotes tumorigenesis and EMT-mediated metastasis through PI3K/AKT pathway in GC. Our study for the first time identified the functions of GRSF1 serving as an oncogene in GC, which may be a potential effective therapeutic target and malignant indicator in GC.

Keywords: EMT; Gastric cancer; Guanine-rich RNA sequence binding factor 1 (GRSF1); PI3K/AKT.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Phosphatidylinositol 3-Kinases / metabolism
  • Poly(A)-Binding Proteins / genetics
  • Poly(A)-Binding Proteins / metabolism*
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*
  • Xenograft Model Antitumor Assays

Substances

  • GRSF1 protein, human
  • Poly(A)-Binding Proteins
  • Proto-Oncogene Proteins c-akt