Silencing of KCNA1 suppresses the cervical cancer development via mitochondria damage

Channels (Austin). 2019 Dec;13(1):321-330. doi: 10.1080/19336950.2019.1648627.

Abstract

Voltage-gated potassium channel subfamily A member 1 (KCNA1/Kv1.1) is an important component of type A potassium channels, which has been found to be involved in various tumors. This study aimed to identify the role of KCNA1 in cervical cancer and explore the related mechanism. The levels of KCNA1 in cervical cancer tissues and cell lines were examined by Western blot and qPCR. Cell proliferation and invasion were assessed by CCK-8 and transwell assays, respectively. Protein levels of Hedgehog (Hhg), Wnt and Notch were detected by Western blot. The mitochondrial capacity was examined by immunostaining with MitoTracker Red CMXRos. KCNA1 was highly expressed in cervical cancer tissues and cell lines, and correlated with poor prognosis. In addition, depletion of KCNA1 suppressed growth, proliferation, migration and invasion of HeLa cells. Moreover, KCNA1 could regulate the Hhg, Wnt and Notch signaling pathways and cause mitochondrial dysfunction. The present study has demonstrated that KCNA1 is an oncogene excessively expressed in cervical cancer, and promotes tumor progression by regulating the Hhg, Wnt and Notch signaling pathways and the mitochondrial capacity. Therefore, our results provide a theoretical basis for the discovery of novel clinical treatment against cervical cancer.

Keywords: Hedgehog (Hhg); Notch signaling pathway; Voltage-gated potassium channel subfamily A member 1 (KCNA1/Kv1.1); Wnt; cervical cancer.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Silencing*
  • HeLa Cells
  • Hedgehogs
  • Humans
  • Kv1.1 Potassium Channel / genetics*
  • Kv1.1 Potassium Channel / metabolism
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Signal Transduction
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / physiopathology

Substances

  • KCNA1 protein, human
  • Kv1.1 Potassium Channel