High expression of hnRNPA1 promotes cell invasion by inducing EMT in gastric cancer

Oncol Rep. 2018 Apr;39(4):1693-1701. doi: 10.3892/or.2018.6273. Epub 2018 Feb 16.

Abstract

Advanced gastric cancer (GC) has a poor prognosis and its treatment strategies are not very efficient. Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) has emerged as a plausible GC marker, however the role and molecular mechanism of hnRNPA1 in cell invasion and migration remains unknown. In the present study, the gene expression across normal and tumor tissue (GENT) database was used to evaluate the mRNA expression of hnRNPA1 in various types of cancer. Western blot analysis (WB) and immunohistochemistry (IHC) were performed to detect the protein expression of hnRNPA1 in GC tissues and adjacent non‑tumor tissues. The expression of multiple oncogenes was detected by western blot analysis and quantitative RT‑PCR in hnRNPA1 overexpressing GC cells. Soft agar colony formation, EdU incorporation, wound healing and invasion assays were applied to verify the role of hnRNPA1 in anchorage‑independent cell growth, migration and invasion in GC cells. Epithelial‑to‑mesenchymal transition (EMT) markers were detected by immunofluorescence, western blot analysis and IHC in vitro. A nude mice model of metastasis carcinoma was established to confirm the role of hnRNPA1 during EMT in vivo. Our results revealed that hnRNPA1 was significantly upregulated in GC tissue. HnRNPA1 overexpression significantly induced cell growth, migration and invasion ability in GC cells. In addition, hnRNPA1 promoted EMT of GC cells in vitro and in vivo. These findings indicated that hnRNPA1 is highly expressed in GC and promoted invasion by inducing EMT transition in GC cells. Thus, hnRNPA1 may be a potential therapeutic target for GC.

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics*
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Heterogeneous Nuclear Ribonucleoprotein A1 / genetics*
  • Humans
  • Male
  • Mice
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • Heterogeneous Nuclear Ribonucleoprotein A1
  • hnRNPA1 protein, human