TY - JOUR
T1 - KCNMA1 expression is downregulated in colorectal cancer via epigenetic mechanisms
AU - Basile, Maria Sofia
AU - Fagone, Paolo
AU - Mangano, Katia
AU - Mammana, Santa
AU - Magro, Gaetano
AU - Salvatorelli, Lucia
AU - Li Destri, Giovanni
AU - La Greca, Gaetano
AU - Nicoletti, Ferdinando
AU - Puleo, Stefano
AU - Pesce, Antonio
PY - 2019/2
Y1 - 2019/2
N2 - 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.
AB - 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.
KW - Colorectal cancer
KW - DNA methylation
KW - Epigenetics
KW - KCNMA1
KW - mir-17-5p
KW - mir-211
KW - mir-31
UR - http://www.scopus.com/inward/record.url?scp=85063641139&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063641139&partnerID=8YFLogxK
U2 - 10.3390/cancers11020245
DO - 10.3390/cancers11020245
M3 - Article
AN - SCOPUS:85063641139
VL - 11
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 2
M1 - 245
ER -