Silencing DNA methyltransferase 1 (DNMT1) inhibits proliferation, metastasis and invasion in ESCC by suppressing methylation of RASSF1A and DAPK.
Our previous study showed DNMT1 is up-regulated in esophageal squamous cell carcinoma (ESCC), which is associated with methylation of tumor suppressors. In the current study, we investigate the role of DNMT1 in ESCC. We found silencing DNMT1 inhibited proliferation, metastasis and invasion of three different ESCC cells, K150, K410 and K450. We also found silencing DNMT1 induced G1 arrest and cell apoptosis in K150, K410 and K450 cells. In vivo study showed silencing DNMT1 suppressed tumor growth in nude mice. In addition, silencing DNMT1 increased expression of tumor suppressor genes, RASSF1A and DAPK, in ESCC cells and ESCC xenograft in nude mice. Moreover, silencing DNMT1 decreased methylation in promoter of RASSF1A and DAPK. In conclusion, our data demonstrated that silencing DNMT1 inhibits proliferation, metastasis and invasion in ESCC by suppressing methylation of RASSF1A and DAPK.
Department of Thoracic & Cardiovascular Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin, China.
Jian
J
Bai
Department of ICU, The Second Affiliated Hospital of Guilin Medical University, Guilin, China.
Xue
X
Zhang
Department of Thoracic & Cardiovascular Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, China.
Kai
K
Hu
Department of Thoracic & Cardiovascular Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin, China.
Bangqing
B
Liu
Department of Thoracic & Cardiovascular Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, China.
Haiyong
H
Wang
Department of Thoracic & Cardiovascular Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, China.
Angui
A
Li
Department of Thoracic & Cardiovascular Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, China.
Feng
F
Lin
Department of Thoracic & Cardiovascular Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin, China.
Lifei
L
Zhang
Department of Thoracic & Cardiovascular Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, China.
Xiaolin
X
Sun
Department of Thoracic & Cardiovascular Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin, China.|Current address:  Department of  Thoracic & Cardiovascular Surgery, The Second Affiliated Hospital of Guilin Medical University, Lingui District, Guilin, China.
Zhenzong
Z
Du
Department of Thoracic & Cardiovascular Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin, China.|Current address:  Department of  Thoracic & Cardiovascular Surgery, The Second Affiliated Hospital of Guilin Medical University, Lingui District, Guilin, China.
Jianfei
J
Song
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D000076123:DNA (Cytosine-5-)-Methyltransferase 1 / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D064550:Death-Associated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D034622:RNA Interference; D000067492:RNAi Therapeutics / Q000379:methods; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; C000619380:DNMT1 protein, human; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases
DAPK; DNA methyltransferase 1; ESCC; RASSF1A; methylation