Estrogen-ERα signaling and DNA hypomethylation co-regulate expression of stem cell protein PIWIL1 in ERα-positive endometrial cancer cells.

Abstract

BACKGROUND:

We previously identified PIWIL1 as an oncogene involved in endometrial carcinogenesis. However, the mechanism of Piwil1 mediated regulation of tumorigenesis remains poorly understood.

METHODS:

The expression levels of target genes in endometrial cancer cells were detected by quantitative reverse transcription-PCR (RT-qPCR) and western blotting. Up- or down-regulation of ERα or PIWIL1 was achieved by transient transfection with expressing plasmids or short hairpin RNA (shRNA). Dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) were used to demonstrate the ERα bound to the half estrogen response element (half-ERE) located in PIWIL1 promoter. The expression of PIWIL1 and ERα in endometrial carcinoma tissues were investigated using immunohistochemistry and RT-qPCR. The proliferation ability of cancer cells were evaluated by MTT. Methylation status of the PIWIL1 promoter was detected by bisulfite sequencing PCR (BSP).

RESULTS:

In the present study, we found that PIWIL1 mediated E2-stimulated cancer cell proliferation. In ERα-positive endometrial cancer cells, we demonstrated that estrogen-ERα signaling significantly up-regulated the expression of PIWIL1, which was mediated by binding of the ERα onto the PIWIL1 promoter. Furthermore, we found that a half-ERE in the PIWIL1 promoter was essential for ERα binding. The PIWIL1 promoter was hypomethylated in ERα-positive endometrial cancer cells. Treatment with 5-aza-deoxycytidine (5-aza-dC) could up-regulate PIWIL1 expression.

CONCLUSIONS:

These findings uncover a novel molecular mechanism by which estrogen-ERα signaling and DNA hypomethylation co-regulate PIWIL1 expression. These findings provide novel insights into the hormonal regulation of PIWIL1 in endometrial cancer and the PIWIL1's role in estrogen-stimulated endometrial carcinogenesis. Video Abstract. (MP4 41319 kb).

• Authors: Zheng Chen, Hua-Jing Yang, Qin Lin, Min-Jiao Zhu, Ying-Ying Yu, Xiao-Ying He, Xiao-Ping Wan
• Journal: Cell communication and signaling : CCS (Cell Commun Signal) Vol. 18 Issue 1 Pg. 84 (06 05 2020) ISSN: 1478-811X [Electronic] England
• PMID: 32503542 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Video-Audio Media)

Chemical References

• Argonaute Proteins
• ESR1 protein, human
• Estrogen Receptor alpha
• Estrogens
• PIWIL1 protein, human

Topics

• Argonaute Proteins (metabolism)
• Carcinogenesis (metabolism)
• Cell Line, Tumor
• Cell Proliferation
• DNA Methylation
• Endometrial Neoplasms (metabolism)
• Estrogen Receptor alpha (metabolism)
• Estrogens (metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans