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Title: PPARγ inhibits ovarian cancer cells proliferation through upregulation of miR-125b

Abstract

miR-125b has essential roles in coordinating tumor proliferation, angiogenesis, invasiveness, metastasis and chemotherapy recurrence. In ovarian cancer miR-125b has been shown to be downregulated and acts as a tumor suppressor by targeting proto-oncogene BCL3. PPARγ, a multiple functional transcription factor, has been reported to have anti-tumor effects through inhibition of proliferation and induction of differentiation and apoptosis by targeting the tumor related genes. However, it is unclear whether miR-125b is regulated by PPARγ in ovarian cancer. In this study, we demonstrated that the miR-125b downregulated in ovarian cancer tissues and cell lines. Ligands-activated PPARγ suppressed proliferation of ovarian cancer cells and this PPARγ-induced growth inhibition is mediated by the upregulation of miR-125b. PPARγ promoted the expression of miR-125b by directly binding to the responsive element in miR-125b gene promoter region. Thus, our results suggest that PPARγ can induce growth suppression of ovarian cancer by upregulating miR-125b which inhibition of proto-oncogene BCL3. These findings will extend our understanding of the function of PPARγ in tumorigenesis and miR-125b may be a therapeutic intervention of ovarian cancer. - Highlights: • miR-125b is down-regulated in ovarian cancer tissues and cells. • PPARγ upregulates miR-125b and downregulates its target gene BCL3 expression. • Silence ofmore » miR-125b attenuates PPARγ-mediated growth suppression of ovarian cancer cells. • PPARγ promotes the transcription of miR-125b via binding to PPARE in miR-125b gene promoter region.« less

Authors:
 [1];  [2];  [3];  [4];  [5]
  1. Department of Obstetrics and Gynecology, Suining Central Hospital, Suining (China)
  2. Department of Gynecology and Obsterics, Jinan Central Hospital, Jinan (China)
  3. Department of Otorhinolaryngolgy, Suining Central Hospital, Suining (China)
  4. Department of Gynecology and Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China)
  5. Department of Gynecology and Obsterics, Zhongshan Hospital, Wuhan (China)
Publication Date:
OSTI Identifier:
22462090
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 462; Journal Issue: 2; Other Information: Copyright (c) 2015 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; ADMINISTRATIVE PROCEDURES; ANGIOGENESIS; ANIMAL TISSUES; APOPTOSIS; CELL PROLIFERATION; CHEMOTHERAPY; COORDINATES; INHIBITION; LIGANDS; METASTASES; NEOPLASMS; ONCOGENES; OVARIES; PLANT GROWTH; PROMOTERS; TRANSCRIPTION; TRANSCRIPTION FACTORS

Citation Formats

Luo, Shuang, E-mail: luoshuangsch@163.com, Wang, Jidong, Ma, Ying, Yao, Zhenwei, and Pan, Hongjuan. PPARγ inhibits ovarian cancer cells proliferation through upregulation of miR-125b. United States: N. p., 2015. Web. doi:10.1016/J.BBRC.2015.04.023.
Luo, Shuang, E-mail: luoshuangsch@163.com, Wang, Jidong, Ma, Ying, Yao, Zhenwei, & Pan, Hongjuan. PPARγ inhibits ovarian cancer cells proliferation through upregulation of miR-125b. United States. doi:10.1016/J.BBRC.2015.04.023.
Luo, Shuang, E-mail: luoshuangsch@163.com, Wang, Jidong, Ma, Ying, Yao, Zhenwei, and Pan, Hongjuan. 2015. "PPARγ inhibits ovarian cancer cells proliferation through upregulation of miR-125b". United States. doi:10.1016/J.BBRC.2015.04.023.
@article{osti_22462090,
title = {PPARγ inhibits ovarian cancer cells proliferation through upregulation of miR-125b},
author = {Luo, Shuang, E-mail: luoshuangsch@163.com and Wang, Jidong and Ma, Ying and Yao, Zhenwei and Pan, Hongjuan},
abstractNote = {miR-125b has essential roles in coordinating tumor proliferation, angiogenesis, invasiveness, metastasis and chemotherapy recurrence. In ovarian cancer miR-125b has been shown to be downregulated and acts as a tumor suppressor by targeting proto-oncogene BCL3. PPARγ, a multiple functional transcription factor, has been reported to have anti-tumor effects through inhibition of proliferation and induction of differentiation and apoptosis by targeting the tumor related genes. However, it is unclear whether miR-125b is regulated by PPARγ in ovarian cancer. In this study, we demonstrated that the miR-125b downregulated in ovarian cancer tissues and cell lines. Ligands-activated PPARγ suppressed proliferation of ovarian cancer cells and this PPARγ-induced growth inhibition is mediated by the upregulation of miR-125b. PPARγ promoted the expression of miR-125b by directly binding to the responsive element in miR-125b gene promoter region. Thus, our results suggest that PPARγ can induce growth suppression of ovarian cancer by upregulating miR-125b which inhibition of proto-oncogene BCL3. These findings will extend our understanding of the function of PPARγ in tumorigenesis and miR-125b may be a therapeutic intervention of ovarian cancer. - Highlights: • miR-125b is down-regulated in ovarian cancer tissues and cells. • PPARγ upregulates miR-125b and downregulates its target gene BCL3 expression. • Silence of miR-125b attenuates PPARγ-mediated growth suppression of ovarian cancer cells. • PPARγ promotes the transcription of miR-125b via binding to PPARE in miR-125b gene promoter region.},
doi = {10.1016/J.BBRC.2015.04.023},
journal = {Biochemical and Biophysical Research Communications},
number = 2,
volume = 462,
place = {United States},
year = 2015,
month = 6
}
  • Highlights: • Expression of ERβ1 was positively correlated with E-cadherin in breast cancer cell. • ERβ1 upregulates E-cadherin expression in breast cancer cell lines. • ERβ1 upregulates E-cadherin expression in a Id1-dependent manner. - Abstract: ERβ1 is a member of the nuclear receptor superfamily of ligand-regulated transcription factors. It plays an important role in regulating the progression of breast cancer. However, the mechanisms of ERβ1 in tumorigenesis, metastasis and prognosis are still not fully clear. In this study, we showed that the expression of ERβ1 was positively correlated with E-cadherin expression in breast cancer cell lines. In addition, we foundmore » that ERβ1 upregulates E-cadherin expression in breast cancer cell lines. Furthermore, we also found that ERβ1 inhibits the migration and invasion of breast cancer cells and upregulated E-cadherin expression in a Id1-dependent manner. Taken together, our study provides further understanding of the molecular mechanism of ERβ1 in tumor metastasis and suggests the feasibility of developing novel therapeutic approaches to target Id1 to inhibit breast cancer metastasis.« less
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  • Highlights: Black-Right-Pointing-Pointer miR-125b is frequently down-regulated in osteosarcoma samples and human osteosarcoma cell lines. Black-Right-Pointing-Pointer Ectopic restoration of miR-125b suppresses cell proliferation and migration in vitro. Black-Right-Pointing-Pointer STAT3 is the direct and functional downstream target of miR-125b. Black-Right-Pointing-Pointer STAT3 can bind to the promoter region of miR-125b and serves as a transactivator. -- Abstract: There is accumulating evidence that microRNAs are involved in multiple processes in development and tumor progression. Abnormally expressed miR-125b was found to play a fundamental role in several types of cancer; however, whether miR-125b participates in regulating the initiation and progress of osteosarcoma still remains unclear.more » Here we demonstrate that miR-125b is frequently down-regulated in osteosarcoma samples and human osteosarcoma cell lines. The ectopic restoration of miR-125b expression in human osteosarcoma cells suppresses proliferation and migration in vitro and inhibits tumor formation in vivo. We further identified signal transducer and activator of transcription 3 (STAT3) as the direct and functional downstream target of miR-125b. Interestingly, we discovered that the expression of miR-125b is regulated by STAT3 at the level of transcription. STAT3 binds to the promoter region of miR-125b in vitro and serves as a transactivator. Taken together, our findings point to an important role in the molecular etiology of osteosarcoma and suggest that miR-125b is a potential target in the treatment of osteosarcoma.« less
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