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

doi:10.3390/cancers11020245

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 journal › Article › peer-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 language	English
Article number	245
Journal	Cancers
Volume	11
Issue number	2
DOIs	https://doi.org/10.3390/cancers11020245
Publication status	Published - Feb 2019

Keywords

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

ASJC Scopus subject areas

Oncology
Cancer Research

Access to Document

10.3390/cancers11020245

Fingerprint Dive into the research topics of 'KCNMA1 expression is downregulated in colorectal cancer via epigenetic mechanisms'. Together they form a unique fingerprint.

Cite this

KCNMA1 expression is downregulated in colorectal cancer via epigenetic mechanisms. / Basile, Maria Sofia; Fagone, Paolo; Mangano, Katia; Mammana, Santa; Magro, Gaetano; Salvatorelli, Lucia; Li Destri, Giovanni; La Greca, Gaetano; Nicoletti, Ferdinando; Puleo, Stefano; Pesce, Antonio.

In: Cancers, Vol. 11, No. 2, 245, 02.2019.

Research output: Contribution to journal › Article › peer-review

@article{08141fc90ca447ef8ed843469581e9eb,

title = "KCNMA1 expression is downregulated in colorectal cancer via epigenetic mechanisms",

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. ",

keywords = "Colorectal cancer, DNA methylation, Epigenetics, KCNMA1, mir-17-5p, mir-211, mir-31",

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

year = "2019",

month = feb,

doi = "10.3390/cancers11020245",

language = "English",

volume = "11",

journal = "Cancers",

issn = "2072-6694",

publisher = "MDPI AG",

number = "2",

}

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 -