Jumonji domain-containing protein 1A promotes cell growth and progression via transactivation of c-Myc expression and predicts a poor prognosis in cervical cancer

Oncotarget. 2016 Dec 20;7(51):85151-85162. doi: 10.18632/oncotarget.13208.

Abstract

Jumonji domain-containing protein 1A (JMJD1A) plays a key role in the development and progression of several cancers. Here, we showed that the expression of JMJD1A is increased in cervical cancer cells and tissues, and that suppression of JMJD1A inhibits proliferation, migration, and invasion of cervical cancer cells. JMJD1A induced transcription of c-Myc, which is essential for cervical cancer growth and progression. Clinical data showed that JMJD1A expression correlated with lymph node metastasis (P=0.031) and FIGO stage (P=0.007). Increased c-Myc levels were associated with tumor differentiation (P=0.007) and FIGO stage (P<0.001). JMJD1A protein levels correlated with c-Myc expression (P<0.001), and high co-expression of the two proteins correlated with a poor prognosis. Survival analysis showed that JMJD1A and c-Myc levels are independent prognostic factors for cervical cancer patients. These results suggest that JMJD1A is a promising therapeutic target in cervical cancer.

Keywords: JMJD1A; c-Myc; cervical cancer; immunohistochemistry; prognosis.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinogenesis
  • Cell Growth Processes
  • Cell Movement
  • Female
  • HeLa Cells
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA, Small Interfering / genetics
  • Survival Analysis
  • Transcriptional Activation
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / mortality

Substances

  • Biomarkers, Tumor
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Small Interfering
  • Jumonji Domain-Containing Histone Demethylases
  • KDM3A protein, human