HNF1B inhibits cell proliferation via repression of SMAD6 expression in prostate cancer

Prostate cancer is the most common malignancy in men in developed countries. In previous study, we identified HNF1B (Hepatocyte Nuclear Factor 1β) as a downstream effector of Enhancer of zeste homolog 2 (EZH2). HNF1B suppresses EZH2‐mediated migration of two prostate cancer cell lines via represses...

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Bibliographic Details
Published in:Journal of cellular and molecular medicine 2020-12, Vol.24 (24), p.14539-14548
Main Authors: Lu, Wei, Sun, Jian, Zhou, Huihui, Wang, Fei, Zhao, Chunchun, Li, Kai, Fan, Caibin, Ding, Guanxiong, Wang, Jianqing
Format: Article
Language:English
Subjects:
Antibodies
CDKN2A
Cell culture
Cell cycle
Cell growth
Cell Line, Tumor
Cell migration
Cell Proliferation
Cyclin D1
Cyclin D1 - genetics
Cyclin D1 - metabolism
Cyclin-Dependent Kinase Inhibitor p16 - metabolism
Datasets
Gene expression
Gene Expression Regulation, Neoplastic
Genomes
Hepatocyte Nuclear Factor 1-beta - genetics
Hepatocyte Nuclear Factor 1-beta - metabolism
HNF1B
Humans
Immunohistochemistry
Laboratories
Male
Malignancy
Mass spectrometry
Original
Peptides
proliferation
Prostate cancer
Prostatic Neoplasms - genetics
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Protein Binding
Proteins
Ribonucleic acid
RNA
Scientific imaging
Signal transduction
SMAD6
Smad6 Protein - genetics
Smad6 Protein - metabolism
Software
Tumor cell lines
Tumor suppressor genes
Tumors
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Summary:Prostate cancer is the most common malignancy in men in developed countries. In previous study, we identified HNF1B (Hepatocyte Nuclear Factor 1β) as a downstream effector of Enhancer of zeste homolog 2 (EZH2). HNF1B suppresses EZH2‐mediated migration of two prostate cancer cell lines via represses the EMT process by inhibiting SLUG expression. Besides, HNF1B expression inhibits cell proliferation through unknown mechanisms. Here, we demonstrated that HNF1B inhibited the proliferation rate of prostate cancer cells. Overexpression of HNF1B in prostate cancer cells led to the arrest of G1 cell cycle and decreased Cyclin D1 expression. In addition, we re‐explored data from ChIP‐sequencing (ChIP‐seq) and RNA‐sequencing (RNA‐seq), and demonstrated that HNF1B repressed Cyclin D1 via direct suppression of SMAD6 expression. We also identified CDKN2A as a HNF1B‐interacting protein that would contribute to HNF1B‐mediated repression of SMAD6 expression. In summary, we provide the novel mechanisms and evidence in support HNF1B as a tumour suppressor gene for prostate cancer.
ISSN:1582-1838
1582-4934
DOI:10.1111/jcmm.16081