Ronghui Yang, Lingkun Zuo, Hui Ma, 等. Downregulation of nc886 contributes to prostate cancer cell invasion and TGFβ1-induced EMT[J]. Genes & Diseases, 2022,9(4).
Ronghui Yang, Lingkun Zuo, Hui Ma, et al. Downregulation of nc886 contributes to prostate cancer cell invasion and TGFβ1-induced EMT[J]. Genes & Diseases, 2022,9(4).
Ronghui Yang, Lingkun Zuo, Hui Ma, 等. Downregulation of nc886 contributes to prostate cancer cell invasion and TGFβ1-induced EMT[J]. Genes & Diseases, 2022,9(4). DOI: 10.1016/j.gendis.2020.12.010.
Ronghui Yang, Lingkun Zuo, Hui Ma, et al. Downregulation of nc886 contributes to prostate cancer cell invasion and TGFβ1-induced EMT[J]. Genes & Diseases, 2022,9(4). DOI: 10.1016/j.gendis.2020.12.010.
Downregulation of nc886 contributes to prostate cancer cell invasion and TGFβ1-induced EMT
摘要
Abstract
Epithelial-to-mesenchymal transition (EMT) activation is important in cancer progression and metastasis. Evidence indicates that
nc886
is a representative Pol III gene that processes microRNA products via Dicer and further downregulates its target gene transforming growth factor- β1 (TGF-β1)
which is the most prominent inducer of EMT in prostate cancer (PC). Consistent with the previous literature
we found that
nc886
downregulation was strongly associated with metastatic behavior and showed worse outcomes in PC patients. However
little is known about the association between
nc886
and the EMT signaling pathway. We developed a PC cell model with stable overexpression of
nc886
and found that
nc886
changed cellular morphology and drove MET. The underlying mechanism may be related to its promotion of SNAIL protein degradation via ubiquitination
but not to its neighboring genes
TGFβ-induced protein (
TGFBI
) and
SMAD5
which are Pol II-transcribed. TGF-β1 also override nc886 promotion of MET via transient suppression the transcription of
nc886
promotion of
TGFBI
or increase in SMAD5 phosphorylation. Both
nc886
inhibition and
TGFBI
activation occur regardless of their methylation status. The literature suggests that MYC inhibition by TGF-β1 is attributed to
nc886
downregulation. We incidentally identified MYC-associated zinc finger protein (MAZ) as a suppressive transcription factor of TGFBI
which is controlled by TGF-β1. We elucidate a new mechanism of TGF-β1 differential control of Pol II and the transcription of its neighboring Pol III gene and identify a new EMT unit consisting of
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相关作者
Malgorzata Czyz
Anna Gajos-Michniewicz
Elizabeth R. Davies
Zijian Xu
Liudi Yao
Yilu Zhou
Juanjuan Li
Aiman Alzetani
相关机构
Department of Molecular Biology of Cancer, Medical University of Lodz
Institute for Life Sciences, University of Southampton
NIHR Southampton Biomedical Research Centre, University Hospital Southampton
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton