Elevated JMJD1A is a novel predictor for prognosis and a potential therapeutic target for gastric cancer

Int J Clin Exp Pathol. 2015 Sep 1;8(9):11092-9. eCollection 2015.

Abstract

Jumonji domain-containing protein 1A (JMJD1A) play a key role in the development and progression of several malignancies. The present study investigated the expression and clinical significance of JMJD1A in gastric cancer. JMJD1A was found to be upregulated in gastric cancer tissues and cell lines. Furthermore, the upregulated expression of JMJD1A was significantly correlated with the results of the invasion depth (P=0.006), lymph node metastatic status (P<0.001), and TNM stage (P<0.001). JMJD1A was also shown to be an independent prognostic predictor of overall survival (HR3.988; 95% CI 1.948-8.167; P<0.001) for patients with gastric cancer. In addition, in vitro experiment revealed that knockdown of JMJD1A expression inhibited the gastric cancer cell proliferation, and further study suggested that JMJD1A knockdown suppressed MAPK pathway via transcriptional downregulation the expression of long noncoding RNA MALAT1. Therefore, we speculated that JMJD1A-MALAT1-MAPK signaling might participate in the JMJD1A-induced cell proliferation of gastric cancer. Collectively, our data demonstrate for the first time that JMJD1A gene has an important regulatory role in gastric carcinogenesis, and could function as a novel prognostic indicator and a potential therapeutic target for gastric cancer.

Keywords: Gastric cancer; JMJD1A; immunohistochemistry; prognosis; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gastrectomy
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Targeted Therapy
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Proportional Hazards Models
  • RNA Interference
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • Signal Transduction
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy
  • Time Factors
  • Transfection
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • MALAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • Jumonji Domain-Containing Histone Demethylases
  • KDM3A protein, human
  • Mitogen-Activated Protein Kinases