title: Piwil1 causes epigenetic alteration of PTEN gene via upregulation of DNA methyltransferase in type I endometrial cancer.
abstract: Piwil1, a member of the Piwi family, has been well demonstrated to mediate tumorigenesis associated with DNA hypermethylation. It has been reported that Piwil1 is overexpressed in various types of cancer, including endometrial cancer. However, the underlying mechanism of Piwil1 in endometrial cancer remains largely unclear. PTEN exerts an important tumor suppressor role in endometrial carcinogenesis. The present study aimed to investigate whether Piwil1 could regulate the expression of PTEN. Herein, we found that Piwil1 could promote the loss of PTEN expression and increase aberrant hypermethylation of PTEN gene promoter in Ishikawa cells. We also found that Piwil1 could regulate the expression of DNA methyltransferase 1 (DNMT1). Silencing DNMT1 gene could upregulate the PTEN gene expression and change the methylation status of PTEN gene promoter in Ishikawa cells. These results suggested that Piwil1 caused the loss of PTEN expression through DNMT1-mediated PTEN hypermethylation. Taken together, these data provide a novel regulatory mechanism of Piwil1 in endometrial cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Che
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Fei-Zhou
authors.initials: FZ
authors.lastname: Jiang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Hui-Hui
authors.initials: HH
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Fang-Yuan
authors.initials: FY
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tong Ji University School of Medicine, Shanghai, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tong Ji University School of Medicine, Shanghai, China. Electronic address: wanxp@sjtu.edu.cn.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Wan
mesh_terms: D060565:Argonaute Proteins / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D019175:DNA Methylation; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000473:pathology; D044127:Epigenesis, Genetic / Q000502:physiology*; D005260:Female; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D060565:Argonaute Proteins; C421088:PIWIL1 protein, human; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: DNA methylation; DNMT1; Endometrial cancer; PTEN; Piwil1