The significance of Runx2 mediating alcohol-induced Brf1 expression and RNA Pol III gene transcription.
Adult
Aged
Breast Neoplasms
/ genetics
Carcinoma, Ductal, Breast
/ genetics
Cell Line, Tumor
Core Binding Factor Alpha 1 Subunit
/ genetics
Ethanol
/ toxicity
Gene Expression Regulation
/ drug effects
Gene Expression Regulation, Neoplastic
Humans
Kaplan-Meier Estimate
Middle Aged
Neoplasm Invasiveness
RNA Polymerase III
/ genetics
Signal Transduction
TATA-Binding Protein Associated Factors
/ genetics
Transcription, Genetic
/ drug effects
Tumor Stem Cell Assay
Up-Regulation
/ genetics
Young Adult
Alcohol
Breast cancer
Brf1
Pol III genes
Runx2
Journal
Chemico-biological interactions
ISSN: 1872-7786
Titre abrégé: Chem Biol Interact
Pays: Ireland
ID NLM: 0227276
Informations de publication
Date de publication:
25 May 2020
25 May 2020
Historique:
received:
24
11
2019
accepted:
10
03
2020
pubmed:
22
3
2020
medline:
28
4
2020
entrez:
22
3
2020
Statut:
ppublish
Résumé
Runx2 (Runt-related transcription factor 2) is a key transcription factor which is associated with osteoblast differentiation and expressed in ER+ (estrogen receptor positive) human breast cancer cell lines. Runx2 also participates in mammary gland development. Deregulation of RNA Pol III genes (polymerase III-dependent genes) is tightly linked to tumor development, while Brf1 (TFIIB-related factor 1) specifically regulates these gene transcription. However, nothing is known about the effect of Runx2 on Brf1 expression and Pol III gene transcription. Expression of Runx2, Brf1 and Pol III genes from the samples of human breast cancer and cell culture model were determined by the assays of RT-qPCR, immunoblot, luciferase reporter activity, immunohistochemistry, chromatin immunoprecipitation and Immunofluorescence. High expression of Runx2 is observed in the cases of breast cancer. The patients of high Runx2 expression at early stages display longer survival period, whereas the cases of high Runx2 at advanced stages reveal faster recurrence. The identification of signaling pathway indicates that JNK1 and c-Jun mediate Runx2 transcription. Repression of Runx2 reduces Brf1 expression and Pol III gene transcription. Further analysis indicates that Runx2 is colocalized with Brf1 in nucleus of breast cancer tissue. Both Runx2 and Brf1 synergistically modulate Pol III gene transcription. These studies indicate that Brf1 overexpression is able to be used as an early diagnosis biomarker of breast cancer, while high Runx2 expression indicates long survival period and faster recurrence. Runx2 mediates the deregulation of Brf1 and Pol III genes and its abnormal expression predicts the worse prognosis of breast cancer.
Identifiants
pubmed: 32198086
pii: S0009-2797(19)31958-1
doi: 10.1016/j.cbi.2020.109057
pmc: PMC7261693
mid: NIHMS1582899
pii:
doi:
Substances chimiques
BRF1 protein, human
0
Core Binding Factor Alpha 1 Subunit
0
TATA-Binding Protein Associated Factors
0
Ethanol
3K9958V90M
RNA Polymerase III
EC 2.7.7.6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
109057Subventions
Organisme : NIAAA NIH HHS
ID : R01 AA024169
Pays : United States
Organisme : NIAAA NIH HHS
ID : R13 AA027725
Pays : United States
Organisme : NIAAA NIH HHS
ID : R21 AA023247
Pays : United States
Informations de copyright
Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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