Up-regulation of UVRAG by HDAC1 inhibition attenuates 5FU-induced cell death in HCT116 colorectal cancer cells

Yoon Kyung Jo; Na Yeon Park; Ji Hyun Shin; Doo Sin Jo; Ji Eun Bae; Eun Sun Choi; Sungho Maeng; Hong Bae Jeon; Seon Ae Roh; Jong Wook Chang; Jin Cheon Kim; Dong Hyung Cho

doi:10.21873/anticanres.12218

Up-regulation of UVRAG by HDAC1 inhibition attenuates 5FU-induced cell death in HCT116 colorectal cancer cells

Yoon Kyung Jo, Na Yeon Park, Ji Hyun Shin, Doo Sin Jo, Ji Eun Bae, Eun Sun Choi, Sungho Maeng, Hong Bae Jeon, Seon Ae Roh, Jong Wook Chang, Jin Cheon Kim, Dong Hyung Cho

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

19 Scopus citations

Abstract

The ultraviolent irradiation resistance-associated gene (UVRAG), a component of the Beclin 1/autophagy-related 6 complex, regulates the autophagy initiation step and functions in the DNA-damage response. UVRAG is frequently mutated in various cancer types, and mutations of UVRAG increase sensitivity to chemotherapy by impairing DNA-damage repair. In this study, we addressed the epigenetic regulation of UVRAG in colorectal cancer cells. UVRAG expression was increased in cells treated with histone deacetylase (HDAC) inhibitors, such as valproic acid and suberoylanilide hydroxamic acid. Down-regulation of HDAC1 enhanced UVRAG expression in colorectal cancer cells. In addition, both chemical and genetic inhibition of HDAC1 reduced the activation of caspase-3 and cytotoxicity in 5-fluorouracil (5FU)-treated cancer cells. In contrast, UVRAG overexpression inhibited caspase activation and cell death in 5FU-treated cells. Taken together, our findings suggest that up-regulation of UVRAG by HDAC1 inhibition potentiates DNA-damage-mediated cell death in colorectal cancer cells.

Original language	English
Pages (from-to)	271-277
Number of pages	7
Journal	Anticancer Research
Volume	38
Issue number	1
DOIs	https://doi.org/10.21873/anticanres.12218
State	Published - Jan 2018

Keywords

5FU
Colorectal cancer
Epigenetics
HDAC1
UVRAG

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10.21873/anticanres.12218

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title = "Up-regulation of UVRAG by HDAC1 inhibition attenuates 5FU-induced cell death in HCT116 colorectal cancer cells",

abstract = "The ultraviolent irradiation resistance-associated gene (UVRAG), a component of the Beclin 1/autophagy-related 6 complex, regulates the autophagy initiation step and functions in the DNA-damage response. UVRAG is frequently mutated in various cancer types, and mutations of UVRAG increase sensitivity to chemotherapy by impairing DNA-damage repair. In this study, we addressed the epigenetic regulation of UVRAG in colorectal cancer cells. UVRAG expression was increased in cells treated with histone deacetylase (HDAC) inhibitors, such as valproic acid and suberoylanilide hydroxamic acid. Down-regulation of HDAC1 enhanced UVRAG expression in colorectal cancer cells. In addition, both chemical and genetic inhibition of HDAC1 reduced the activation of caspase-3 and cytotoxicity in 5-fluorouracil (5FU)-treated cancer cells. In contrast, UVRAG overexpression inhibited caspase activation and cell death in 5FU-treated cells. Taken together, our findings suggest that up-regulation of UVRAG by HDAC1 inhibition potentiates DNA-damage-mediated cell death in colorectal cancer cells.",

keywords = "5FU, Colorectal cancer, Epigenetics, HDAC1, UVRAG",

author = "Jo, {Yoon Kyung} and Park, {Na Yeon} and Shin, {Ji Hyun} and Jo, {Doo Sin} and Bae, {Ji Eun} and Choi, {Eun Sun} and Sungho Maeng and Jeon, {Hong Bae} and Roh, {Seon Ae} and Chang, {Jong Wook} and Kim, {Jin Cheon} and Cho, {Dong Hyung}",

year = "2018",

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doi = "10.21873/anticanres.12218",

language = "English",

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pages = "271--277",

journal = "Anticancer Research",

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AU - Jo, Yoon Kyung

AU - Park, Na Yeon

AU - Shin, Ji Hyun

AU - Jo, Doo Sin

AU - Bae, Ji Eun

AU - Choi, Eun Sun

AU - Maeng, Sungho

AU - Jeon, Hong Bae

AU - Roh, Seon Ae

AU - Chang, Jong Wook

AU - Kim, Jin Cheon

AU - Cho, Dong Hyung

PY - 2018/1

Y1 - 2018/1

N2 - The ultraviolent irradiation resistance-associated gene (UVRAG), a component of the Beclin 1/autophagy-related 6 complex, regulates the autophagy initiation step and functions in the DNA-damage response. UVRAG is frequently mutated in various cancer types, and mutations of UVRAG increase sensitivity to chemotherapy by impairing DNA-damage repair. In this study, we addressed the epigenetic regulation of UVRAG in colorectal cancer cells. UVRAG expression was increased in cells treated with histone deacetylase (HDAC) inhibitors, such as valproic acid and suberoylanilide hydroxamic acid. Down-regulation of HDAC1 enhanced UVRAG expression in colorectal cancer cells. In addition, both chemical and genetic inhibition of HDAC1 reduced the activation of caspase-3 and cytotoxicity in 5-fluorouracil (5FU)-treated cancer cells. In contrast, UVRAG overexpression inhibited caspase activation and cell death in 5FU-treated cells. Taken together, our findings suggest that up-regulation of UVRAG by HDAC1 inhibition potentiates DNA-damage-mediated cell death in colorectal cancer cells.

AB - The ultraviolent irradiation resistance-associated gene (UVRAG), a component of the Beclin 1/autophagy-related 6 complex, regulates the autophagy initiation step and functions in the DNA-damage response. UVRAG is frequently mutated in various cancer types, and mutations of UVRAG increase sensitivity to chemotherapy by impairing DNA-damage repair. In this study, we addressed the epigenetic regulation of UVRAG in colorectal cancer cells. UVRAG expression was increased in cells treated with histone deacetylase (HDAC) inhibitors, such as valproic acid and suberoylanilide hydroxamic acid. Down-regulation of HDAC1 enhanced UVRAG expression in colorectal cancer cells. In addition, both chemical and genetic inhibition of HDAC1 reduced the activation of caspase-3 and cytotoxicity in 5-fluorouracil (5FU)-treated cancer cells. In contrast, UVRAG overexpression inhibited caspase activation and cell death in 5FU-treated cells. Taken together, our findings suggest that up-regulation of UVRAG by HDAC1 inhibition potentiates DNA-damage-mediated cell death in colorectal cancer cells.

KW - 5FU

KW - Colorectal cancer

KW - Epigenetics

KW - HDAC1

KW - UVRAG

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Up-regulation of UVRAG by HDAC1 inhibition attenuates 5FU-induced cell death in HCT116 colorectal cancer cells

Abstract

Keywords

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