MicroRNA-27a Indirectly Regulates Estrogen Receptor α Expression and Hormone Responsiveness in MCF-7 Breast Cancer Cells

Li, Xiangrong; Mertens‐Talcott, Susanne U.; Zhang, Shu; Kim, Kyounghyun; Ball, J. K.; Safe, Stephen

doi:10.1210/en.2009-1150

Cited by 86 publications

(61 citation statements)

References 42 publications

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“…It has also shown suggestive levels of association in hypothyroidism (32), atopic dermatitis (33) and self-reported allergy (34). ZBTB10 is thought to regulate specificity proteins Sp1, Sp3 and Sp4 (35,36); in cell culture studies, it is suppressed by ROSmicroRNA27a, thereby enhancing estrogen receptor α expression and mediating estrogen effects (36). Potential immunoregulation could either be through Sp1 (critical for interleukin [IL]-10 and CD40 responses) (37,38) or indirectly via estrogen effects on autoimmunity (39,40).…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study of Late-Onset Myasthenia Gravis: Confirmation of TNFRSF11A and Identification of ZBTB10 and Three Distinct HLA Associations

Seldin

Alkhairy

Lee

et al. 2015

Mol Med

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Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study of Late-Onset Myasthenia Gravis: Confirmation of TNFRSF11A and Identification of ZBTB10 and Three Distinct HLA Associations

Seldin

Alkhairy

Lee

et al. 2015

Mol Med

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“…Li et al confirmed that antisense microRNA-27a and overexpression of ZBTB10 blocked estrogen-induced transactivation in breast cancer (15). These studies suggest that microRNA-27a: ZBTB10-specificity protein pathway mediates hormone-induced bio-function.…”

Section: Introductionmentioning

confidence: 90%

The microRNA-27a: ZBTB10-specificity protein pathway is involved in follicle stimulating hormone-induced VEGF, Cox2 and survivin expression in ovarian epithelial cancer cells

Lai

Zhang

et al. 2012

International Journal of Oncology

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Abstract. Previously, we demonstrated that follicle stimulating hormone (FSH) enhanced VEGF expression and facilitated ovarian cancer angiogenesis via the PI3K/AKT signaling pathway. In this study, we further investigated the involvement of microRNA-27a: ZBTB10-specificity protein pathway in the mechanism of FSH-induced VEGF, Cox2 and survivin expression. Treatment with FSH resulted in significant increase in the expression of VEGF, Cox2, survivin, Sp1 proteins and microRNA-27a in a dose-dependent manner, whereas reverse protein expression pattern was observed in ZBTB10. Downregulation of microRNA-27a using antisense microRNA27a blocked FSH-induced VEGF, Cox2 and survivin expression. Overexpression of ZBTB10 also attenuated the FSH-induced expression of these molecules. The enhanced expression of VEGF, Cox2 and survivin was also abolished by knocking down Sp1 using small interfering RNA. Collectively, these results indicated that stimulation of ovarian cancer cell VEGF, Cox2 and survivin expression by FSH involves the microRNA-27a: ZBTB10-specificity protein pathway. IntroductionOvarian cancer is the most lethal gynecological malignancy in women because of occult metastases within the peritoneal cavity and the advanced stage at detection when curative therapy is ineffective. Approximately 80-90% ovarian cancer is origin from ovarian surface epithelium. The etiology of ovarian epithelial cancer (OEC) remains to be clarified, multiple factors involved in OEC development, for example, hormonal, environmental and genetic factors may play a role. Currently, the gonadotropin theory of ovarian cancer proposes that elevated serum gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), contribute significantly to the development of ovarian cancer. In previous study, Choi et al have reported that FSH enhanced ovarian cancer cells proliferation and invasion by PI3K/AKT signal pathway (1,2). Recent study in our laboratory demonstrated that FSH inhibits ovarian cancer cell apoptosis by upregulating survivin and downregulating PDCD6 and DR5 (3). These studies indicate FSH plays an important role in OEC occurrence, especially in postmenopausal women. In our previous work, it was also reported that activation of the PI3K/AKT pathway mediates FSH-stimulated VEGF expression in ovarian serous cystadenocarcinoma (4). This study also showed that survivin and HIF1α are involved in FSH-mediated VEGF expression by PI3K/ AKT signal pathway. Survivin is a member of the inhibitor of apoptosis protein (IAP) family, in addition to the anti-apoptosis function, the role of survivin to regulate VEGF expression has been described in various tumor cell types (5,6). These factors contribute to tumor angiogenesis. Inflammation also facilitate tumor angiogenesis, Cox2 is an important effector molecule of inflammation and was reported to be involve in VEGF expression and tumor angiogenesis. In our recent study, it was found FSH could significantly upregulate Cox2 expression in a dose-dependent manner (unpublish data). Althoug...

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“…Furthermore, many features of previously mentioned syndromes (i.e., chromosomal instability, cancer) can be explained by problems associated to chromosome segrega- tion and mitosis, which might result from improper p44 downregulation. In that regard, the overexpression of miR-27a in several cancer types has been proposed to promote oncogenic features, supporting that improper transcriptional shutdown/ inefficient DNA repair might lead to improper resolution of mitosis and cancer (32,(35)(36)(37).…”

Section: Discussionmentioning

confidence: 95%

MicroRNA-27a regulates basal transcription by targeting the p44 subunit of general transcription factor IIH

Portal

2011

Proc. Natl. Acad. Sci. U.S.A.

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General transcription factor IIH (TFIIH) is a complex RNA polymerase II basal transcription factor comprising 10 different polypeptides that display activities involved in transcription and DNA repair processes. Although biochemical studies have uncovered TFIIH importance, little is known about how the mRNAs that code for TFIIH subunits are regulated. Here it is shown that mRNAs encoding seven of the TFIIH subunits (p34, p44, p52, p62, XPB, CDK7, and p8) are regulated at the posttranscriptional level in a Dicer-dependent manner. Indeed, abolition of the miRNA pathway induces abnormal accumulation, stabilization, and translational activation of these seven mRNAs. Herein, miR-27a was identified as a key regulator of p44 mRNA. Moreover, miR-27a was shown to destabilize the p44 subunit of the TFIIH complex during the G2-M phase, thereby modulating the transcriptional shutdown observed during this transition. This work is unique in providing a demonstration of global transcriptional regulation through the action of a single miRNA.T o maintain cellular homeostasis, cells have evolved a myriad of specialized pathways, among which basal transcription and DNA repair play crucial roles. Both mechanisms are mainly regulated by the multisubunit complex termed TFIIH (general transcription factor IIH) formed by two modules, the core and the CAK [cyclin-dependent kinase (CDK)-activated kinase], each displaying distinguishable activities and differential protein composition (1-3). Whereas the core is constituted by seven polypeptides (p34, p44, p52, p62, XPB, XPD, and p8) and is indispensable for transcription and DNA repair (4), the CAK contains only three proteins (CDK7, CycH, and MAT1) and is required to modulate transcription by phosphorylating the carboxyl terminal domain of RNA polymerase II (5). Moreover, the CAK module regulates cellcycle progression by phosphorylating CDKs during G2-M transition in an autonomous fashion (6).Mutations in different TFIIH subunits lead to severe clinical disorders that range from mental retardation to cancer predisposition. This predisposition is manifested in patients displaying three clinically well-characterized syndromes-Xeroderma Pigmentosum, Cockaine syndrome, and Trichothiodystrophyhighlighting the importance of maintaining TFIIH integrity (7-9). Lessons learned from mutations encountered on patients helped to unravel which activities of TFIIH were modified in different clinical contexts. However, it has not been possible either to link specific mutations with a particular syndrome or with clinical severity (10-12). Nevertheless, all three clinical anomalies are taught, in principle, to be caused by diminished transcriptional and DNA repair activities often associated with reduced TFIIH stability. In vitro-obtained data show that naturally occurring mutations in XPD or p44 that alter the XPD/p44 or p44/p62 interaction may affect the composition of TFIIH by decreasing levels of XPD and CAK subunits associated with the core. On the other hand, mutations in XPB and p52 may prevent XPB...

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MicroRNA-27a Indirectly Regulates Estrogen Receptor α Expression and Hormone Responsiveness in MCF-7 Breast Cancer Cells

Cited by 86 publications

References 42 publications

Genome-Wide Association Study of Late-Onset Myasthenia Gravis: Confirmation of TNFRSF11A and Identification of ZBTB10 and Three Distinct HLA Associations

Genome-Wide Association Study of Late-Onset Myasthenia Gravis: Confirmation of TNFRSF11A and Identification of ZBTB10 and Three Distinct HLA Associations

The microRNA-27a: ZBTB10-specificity protein pathway is involved in follicle stimulating hormone-induced VEGF, Cox2 and survivin expression in ovarian epithelial cancer cells

MicroRNA-27a regulates basal transcription by targeting the p44 subunit of general transcription factor IIH

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