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Title: Regulation of the P2X7R by microRNA-216b in human breast cancer

Abstract

Highlights: • We suggest the expression level of miR-216b and P2X7R in breast cancer tissues and cell lines. • We demonstrated that miR-216b directly targets and inhibits P2X7R. • We suggested miR-216b can attenuate ATP/P2X7R signaling pathways and induced Bcl-2/caspase-3 pathway. - Abstract: Breast cancer is the most common cancer in women around the world. However, the molecular mechanisms underlying breast cancer pathogenesis are only partially understood. Here, in this study, we found that P2X7R was up-regulated and miR-216b was down-regulated in breast cancer cell lines and tissues. Using bioinformatic analysis and 3′UTR luciferase reporter assay, we determined P2X7R can be directly targeted by miR-216b, which can down-regulate endogenous P2X7R mRNA and protein levels. Ectopic expression of miR-216b mimics leads to inhibited cell growth and apoptosis, while blocking expression of the miR-216b results in increased cell proliferation. Furthermore, our findings demonstrate that knockdown of P2X7R promotes apoptosis in breast cancer cells through down-regulating Bcl-2 and increasing the cleavage caspase-3 protein level. Finally, we confirmed that down-regulation of miR-216b in breast cancer is inversely associated with P2X7R expression level. Together, these findings establish miR-216b as a novel regulator of P2X7R and a potential therapeutic target for breast cancer.

Authors:
 [1];  [2];  [3]; ; ; ; ; ;  [1];  [4]
  1. Department of Breast and Thyroid, Jinan Military General Hospital, Jinan 250031, Shandong Province (China)
  2. Department of General Surgery, Jinan Military General Hospital, Jinan 250031, Shandong Province (China)
  3. Department of General Surgery, Shanghai Ninth People’s Hospital, Shanghai 200011 (China)
  4. Department of Oncology, Jinan Military General Hospital, Jinan 250031, Shandong Province (China)
Publication Date:
OSTI Identifier:
22416743
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 452; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; APOPTOSIS; ATP; BORON CHLORIDES; CELL PROLIFERATION; CHANNELING; HUMAN POPULATIONS; LUCIFERASE; MAMMARY GLANDS; MESSENGER-RNA; NEOPLASMS; PATHOGENESIS; WOMEN

Citation Formats

Zheng, Luming, Zhang, Xukui, Yang, Feng, Zhu, Jian, Zhou, Peng, Yu, Fang, Hou, Lei, Xiao, Lei, He, Qingqing, and Wang, Baocheng, E-mail: wangbaocheng4w4@163.com. Regulation of the P2X7R by microRNA-216b in human breast cancer. United States: N. p., 2014. Web. doi:10.1016/J.BBRC.2014.07.101.
Zheng, Luming, Zhang, Xukui, Yang, Feng, Zhu, Jian, Zhou, Peng, Yu, Fang, Hou, Lei, Xiao, Lei, He, Qingqing, & Wang, Baocheng, E-mail: wangbaocheng4w4@163.com. Regulation of the P2X7R by microRNA-216b in human breast cancer. United States. doi:10.1016/J.BBRC.2014.07.101.
Zheng, Luming, Zhang, Xukui, Yang, Feng, Zhu, Jian, Zhou, Peng, Yu, Fang, Hou, Lei, Xiao, Lei, He, Qingqing, and Wang, Baocheng, E-mail: wangbaocheng4w4@163.com. Fri . "Regulation of the P2X7R by microRNA-216b in human breast cancer". United States. doi:10.1016/J.BBRC.2014.07.101.
@article{osti_22416743,
title = {Regulation of the P2X7R by microRNA-216b in human breast cancer},
author = {Zheng, Luming and Zhang, Xukui and Yang, Feng and Zhu, Jian and Zhou, Peng and Yu, Fang and Hou, Lei and Xiao, Lei and He, Qingqing and Wang, Baocheng, E-mail: wangbaocheng4w4@163.com},
abstractNote = {Highlights: • We suggest the expression level of miR-216b and P2X7R in breast cancer tissues and cell lines. • We demonstrated that miR-216b directly targets and inhibits P2X7R. • We suggested miR-216b can attenuate ATP/P2X7R signaling pathways and induced Bcl-2/caspase-3 pathway. - Abstract: Breast cancer is the most common cancer in women around the world. However, the molecular mechanisms underlying breast cancer pathogenesis are only partially understood. Here, in this study, we found that P2X7R was up-regulated and miR-216b was down-regulated in breast cancer cell lines and tissues. Using bioinformatic analysis and 3′UTR luciferase reporter assay, we determined P2X7R can be directly targeted by miR-216b, which can down-regulate endogenous P2X7R mRNA and protein levels. Ectopic expression of miR-216b mimics leads to inhibited cell growth and apoptosis, while blocking expression of the miR-216b results in increased cell proliferation. Furthermore, our findings demonstrate that knockdown of P2X7R promotes apoptosis in breast cancer cells through down-regulating Bcl-2 and increasing the cleavage caspase-3 protein level. Finally, we confirmed that down-regulation of miR-216b in breast cancer is inversely associated with P2X7R expression level. Together, these findings establish miR-216b as a novel regulator of P2X7R and a potential therapeutic target for breast cancer.},
doi = {10.1016/J.BBRC.2014.07.101},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 452,
place = {United States},
year = {Fri Sep 12 00:00:00 EDT 2014},
month = {Fri Sep 12 00:00:00 EDT 2014}
}
  • No abstract prepared.
  • Fatty acid synthase (FAS) is a major lipogenic enzyme catalyzing the synthesis of long-chain saturated fatty acids. Most breast cancers require lipogenesis for growth. Here, we demonstrated the effects of theanaphthoquinone (TNQ), a member of the thearubigins generated by the oxidation of theaflavin (TF-1), on the expression of FAS in human breast cancer cells. TNQ was found to suppress the EGF-induced expression of FAS mRNA and FAS protein in MDA-MB-231 cells. Expression of FAS has previously been shown to be regulated by the SREBP family of transcription factors. In this study, we demonstrated that the EGF-induced nuclear translocation of SREBP-1more » was blocked by TNQ. Moreover, TNQ also modulated EGF-induced ERK1/2 and Akt phosphorylation. Treatment of MDA-MB-231 cells with PI 3-kinase inhibitors, LY294002 and Wortmannin, inhibited the EGF-induced expression of FAS and nuclear translocation of SREBP-1. Treatment with TNQ inhibited EGF-induced EGFR/ErbB-2 phosphorylation and dimerization. Furthermore, treatment with kinase inhibitors of EGFR and ErbB-2 suggested that EGFR/ErbB-2 activation was involved in EGF-induced FAS expression. In constitutive FAS expression, TNQ inhibited FAS expression and Akt autophosphorylation in BT-474 cells. The PI 3-kinase inhibitors and tyrosine kinase inhibitors of EGFR and ErbB-2 also reduced constitutive FAS expression. In addition, pharmacological blockade of FAS by TNQ decreased cell viability and induced cell death in BT-474 cells. In summary, our findings suggest that TNQ modulates FAS expression by the regulation of EGFR/ErbB-2 pathways and induces cell death in breast cancer cells.« less
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