Overexpression of KCNJ4 correlates with cancer progression and unfavorable prognosis in lung adenocarcinoma

J Biochem Mol Toxicol. 2019 Apr;33(4):e22270. doi: 10.1002/jbt.22270. Epub 2018 Dec 4.

Abstract

KCNJ4 (potassium voltage-gated channel subfamily J member 4) belongs to the inward rectifier potassium channel family, which is inhibited by novel anticancer agents. However, the biologic significance of KCNJ4 in lung adenocarcinoma (LADC) is largely unknown. Therefore, in this study, we evaluated the expression, clinical correlation, and prognostic value of KCNJ4 in LADC and normal lung tissues according to data from The Cancer Genome Atlas datasets. A small interfering RNA (siRNA)-mediated technology was used to inhibit the expression level of KCNJ4. Cell counting kit-8 and plate colony formation assays were used to measure cell proliferation. Wound-healing and transwell assays were applied to detect cell mobility and metastasis. Quantitative real-time polymerase chain reaction and western blot analysis were used to examine messenger RNA and protein expressions, respectively. It was found that KCNJ4 was significantly upregulated in LADC tissues and cells. The high level of KCNJ4 predicted shorter overall survival and was identified as an independent prognostic factor in patients with LADC. siRNA-mediated KCNJ4 silencing impeded LADC cell proliferation, migration, and invasion. Knockdown of KCNJ4 suppressed the expression of phosphorylated mitogen-activated protein kinase/extracellular signal regulated kinase (p-MEK) and phosphorylated extracellular signal-regulated kinase (p-ERK). Collectively, these results shed some light on the contribution of KCNJ4 functioning as a significant player in LADC, implying that KCNJ4 might be a valuable prognostic biomarker and a potential therapeutic target for LADC treatment.

Keywords: invasion; lung adenocarcinoma (LADC); migration; potassium voltage-gated channel subfamily J member 4 (KCNJ4); prognosis; proliferation.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Potassium Channels, Inwardly Rectifying / genetics*
  • Prognosis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction

Substances

  • KCNJ4 protein, human
  • Potassium Channels, Inwardly Rectifying
  • RNA, Messenger