KCNMA1 expression is downregulated in colorectal cancer via epigenetic mechanisms

Maria Sofia Basile, Paolo Fagone, Katia Mangano, Santa Mammana, Gaetano Magro, Lucia Salvatorelli, Giovanni Li Destri, Gaetano La Greca, Ferdinando Nicoletti, Stefano Puleo, Antonio Pesce

Research output: Contribution to journalArticlepeer-review

Abstract

KCNMA1 is a gene located at 10q22 that encodes the pore-forming α-subunit of the large-conductance Ca 2+ -activated K + channel. KCNMA1 is down-regulated in gastric carcinoma tumors, through hypermethylation of its promoter. In the present study, we have evaluated the expression levels of KCNMA1 both in a mouse model of Colorectal Cancer (CRC) and in human CRC samples. Additionally, epigenetic mechanisms of KCNMA1 gene regulation were investigated. We observed a significant down-regulation of KCNMA1 both in a human and mouse model of CRC. No differences in KCNMA1 levels were, however, observed at different TNM stages. We also wanted to determine whether the modulation in KCNMA1 was dependent on epigenetic mechanisms. A statistically significant inverse correlation between KCNMA1 expression and mir-17-5p levels was observed in patients with CRC. Furthermore, in the tumor samples, we found a significant hypermethylation of the promoter, in the loci cg24113782 and cg25655799, compared to healthy tissue. Overall, our data suggest the possible use of KCNMA1 as a therapeutic target in the early stages of CRC.

Original languageEnglish
Article number245
JournalCancers
Volume11
Issue number2
DOIs
Publication statusPublished - Feb 2019

Keywords

  • Colorectal cancer
  • DNA methylation
  • Epigenetics
  • KCNMA1
  • mir-17-5p
  • mir-211
  • mir-31

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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