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J Biol Chem. 2016 May 13;291(20):10646-58. doi: 10.1074/jbc.M116.723239. Epub 2016 Mar 8.

The Role of PIWIL4, an Argonaute Family Protein, in Breast Cancer.

Author information

1
From the School of Life Science and Technology and Shanghai Institute of Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China and.
2
the Yale Stem Cell Center and Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520.
3
Shanghai Institute of Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China and.
4
Shanghai Institute of Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China and haifan.lin@yale.edu.
5
From the School of Life Science and Technology and Shanghai Institute of Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China and the Yale Stem Cell Center and Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520 liush@shanghaitech.edu.cn.

Abstract

P-element-induced wimpy testis (PIWI) proteins bind to PIWI-interacting RNAs and play key roles in the biogenesis and functions of PIWI-interacting RNAs. It has been reported that PIWI proteins are essential for stem cell self-renewal and germline development in diverse organisms and that they are ectopically expressed in multiple forms of cancer. However, the role of PIWI in cancer remains elusive. Here we report that one of the four PIWI proteins in humans, PIWIL4, is highly expressed in both breast cancer tissues and the cytoplasm of MDA-MB-231 cells derived from breast cancer. Reducing PIWIL4 expression drastically impairs the migration ability of MDA-MB-231 cells, significantly increases their apoptosis, and mildly affects their proliferation. Our transcriptome and proteome analysis reveal that these functions are at least partially achieved via the PIWIL4 regulation of TGF-β and FGF signaling pathways and MHC class II proteins. These findings suggest that PIWIL4 may serve as a potential therapeutic target for breast cancer.

KEYWORDS:

Argonaute; TGF-β; cancer; metastasis; migration

PMID:
26957540
PMCID:
PMC4865913
DOI:
10.1074/jbc.M116.723239
[Indexed for MEDLINE]
Free PMC Article
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