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Targeted demethylation of the SLC5A7 promotor inhibits colorectal cancer progression.
Li, Yang; Liu, Baike; Yin, Xiaonan; Jiang, Zhiyuan; Fang, Chao; Chen, Na; Zhang, Bo; Dai, Lei; Yin, Yuan.
Afiliación
  • Li Y; Department of Gastrointestinal Surgery, Guang'an People's Hospital, Guang'an, 638500, Sichuan, People's Republic of China.
  • Liu B; Department of Gastrointestinal Surgery, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
  • Yin X; Department of Gastrointestinal Surgery, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
  • Jiang Z; Department of Gastrointestinal Surgery, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
  • Fang C; Department of Gastrointestinal Surgery, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
  • Chen N; Department of Gastrointestinal Surgery, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
  • Zhang B; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, Sichuan, People's Republic of China.
  • Dai L; School of Pharmacy, Chengdu Medical College, Chengdu, 610500, People's Republic of China.
  • Yin Y; Department of Gastrointestinal Surgery, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China. hxwcwk@126.com.
Clin Epigenetics ; 14(1): 92, 2022 07 20.
Article en En | MEDLINE | ID: mdl-35858918
BACKGROUND: SLC5A7 (solute carrier family 5 member 7), also known as choline transporter 1 (CHT1), is downregulated in colorectal cancer (CRC) and functions as a tumor suppressor. However, the mechanisms underlying the inactivation of SLC5A7 in CRC remain to be elucidated. RESULTS: In the present study, two broad-spectrum demethylation agents (azacitidine and decitabine) employed to treat CRC cells significantly upregulated SLC5A7 expression. Further results based on the CRC cohort and TCGA database indicated that SLC5A7 promoter methylation inversely correlated with SLC5A7 expression, and the status of SLC5A7 promotor methylation showed a promising prognostic value for patients with CRC. Next, the dCas9-multiGCN4/scFv-TET1CD-based precision demethylation system was constructed, which could significantly and specifically promote SLC5A7 expression in CRC cells through sgRNA targeting the SLC5A7 promoter. Both in vitro and in vivo experiments demonstrated that targeted demethylation of SLC5A7 by dCas9-multiGCN4/scFv-TET1CD-sgSLC5A7 inhibited tumor growth by stabilizing p53 and regulating downstream targets. CONCLUSIONS: Collectively, DNA promoter methylation caused inactivation of SLC5A7 in CRC, and targeted demethylation of SLC5A7 might be a therapeutic target for CRC and other cancers.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Simportadores Límite: Humans Idioma: En Revista: Clin Epigenetics Año: 2022 Tipo del documento: Article Pais de publicación: Alemania
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Simportadores Límite: Humans Idioma: En Revista: Clin Epigenetics Año: 2022 Tipo del documento: Article Pais de publicación: Alemania