TR4 Nuclear Receptor Alters the Prostate Cancer CD133+ Stem/Progenitor Cell Invasion via Modulating the EZH2-Related Metastasis Gene Expression

Zhu, Jin; Yang, Dian; Sun, Yin; Qiu, Xiaoyu; Chang, Hong-Chiang; Li, Gonghui; Shan, Yuxi; Chang, Chawnshang

doi:10.1158/1535-7163.mct-14-0971

Cited by 16 publications

(10 citation statements)

References 49 publications

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“…Furthermore, the TR4–shRNA effect on enhancing PCa radiation sensitivity can be interrupted by adding miR-212-3p inhibitor. Together, these results conclude that targeting TR4 can increase the IR sensitivity in PCa ( 26 ).…”

Section: Tr4 Role In Pca Chemotherapy and Radiation Therapysupporting

confidence: 56%

“…Adding back EZH2 in the TR4–shRNA PCa cell lines can partially interrupt the TR4–shRNA suppression effect on PCa cells invasion. Together, these results suggest that EZH2 is another TR4 target that plays a critical role in the PCa S/P cell invasion ( 26 ).…”

Section: Tr4 Role In Pca Metastasismentioning

confidence: 88%

“…Moreover, Zhu et al demonstrated that TR4 plays a positive role in PCa stem/progenitor (S/P) cell invasion ( 26 ), and targeting TR4 with shRNA significantly suppressed PCa S/P cell invasion both in vitro and in vivo . Mechanism dissection using ChIP and luciferase assays found that TR4 transcriptionally regulates the oncogene EZH2 .…”

Section: Tr4 Role In Pca Metastasismentioning

confidence: 99%

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TR4 Nuclear Receptor Different Roles in Prostate Cancer Progression

Lin

Yang

et al. 2015

Front. Endocrinol.

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Nuclear receptors are important to maintain the tissue homeostasis. Each receptor is tightly controlled and under a very complicated balance. In this review, we summarize the current findings regarding the nuclear receptor TR4 and its role in prostate cancer (PCa) progression. In general, TR4 can inhibit the PCa carcinogenesis. However, when PPARγ is knocked out, activation of TR4 can have an opposite effect to promote the PCa carcinogenesis. Clinical data also indicates that higher TR4 expression is found in PCa tissues with high Gleason scores compared to those tissues with low Gleason scores. In vitro and in vivo studies show that TR4 can promote PCa progression. Mechanism dissection indicates that TR4 inhibits PCa carcinogenesis through regulating the tumor suppressor ATM to reduce DNA damages. On the other hand, in the absence of PPARγ, TR4 tends to increase the stem cell population and epithelial–mesenchymal transition (EMT) via regulating CCL2, Oct4, EZH2, and miRNA-373-3p expression that results in increased PCa carcinogenesis. In opposition to PCa initiation, TR4 can increase PCa metastasis via modulating the CCL2 signals. Finally, targeting TR4 enhances the chemotherapy and radiation therapy sensitivity in PCa. Together, these data suggest TR4 is a key player to control PCa progression, and targeting TR4 with small molecules may provide us a new and better therapy to suppress PCa progression.

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Section: Tr4 Role In Pca Chemotherapy and Radiation Therapysupporting

confidence: 56%

Section: Tr4 Role In Pca Metastasismentioning

confidence: 88%

Section: Tr4 Role In Pca Metastasismentioning

confidence: 99%

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TR4 Nuclear Receptor Different Roles in Prostate Cancer Progression

Lin

Yang

et al. 2015

Front. Endocrinol.

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“…In breast cancer, NR2C2 interacts with estrogen receptor to inhibit MCF-7 cell proliferation [29]. NR2C2 is highly expressed in CD133+ prostate cancer stem/progenitor cells and promoted their invasion through enhancer of zeste homolog 2 signaling involving several metastasis-associated genes such as NOTCH1, SLUG, transforming growth factor β 1, and matrix metalloproteinase 9 [30]. NR2C2 was overexpressed in pituitary adenoma and promoted ACTH secretion, cell proliferation, and tumor invasion [31].…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Study of NR2C2, BTG2, TBX19, and CDK2 Expression in 31 Paired Primary/Recurrent Nonfunctioning Pituitary Adenomas

Yao¹,

Zhang

Wu³

et al. 2019

International Journal of Endocrinology

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This study investigated potential markers for predicting nonfunctioning pituitary adenoma (NFPA) invasion and recurrence by high-throughput tissue microarray analyses. We retrospectively studied two groups of patients: 60 nonrecurrent NFPA cases that included noninvasion and invasion subtypes and 43 recurrent cases that included primary NFPA. A total of 31 paired patient samples were evaluated (12 patients with one surgery and 31 who had undergone two operations, with both tumors analyzed). Expressions of nuclear receptor subfamily 2 group C member 2 (NR2C2), B cell translocation gene 2, T-box-19 (TBX19), and cyclin-dependent kinase 2 (CDK2) in surgically resected specimens were assessed by immunohistochemistry. The relationships between marker expression and clinical characteristics including age, sex, tumor volume, and follow-up time were analyzed. Tumor volume and invasion as well as follow-up time were significantly associated with invasion and recurrence (P < 0.01). Of the 60 nonrecurrent samples, 15/41 and 13/19 showed high NR2C2 expression in the noninvasion and invasion groups, respectively (χ2 =5.287, P = 0.021). NR2C2 was also overexpressed in 43 primary recurrent cases (χ2 =5.433, P = 0.02), whereas CDK2 (χ2 = 11.242, P = 0.001) and TBX19 (χ2 = 4.875, P = 0.027) were downregulated. In the 31 paired samples, NR2C2 was more highly expressed in the recurrent as compared to the primary tumor. High NR2C2 expression was associated with NFPA invasion, recurrence, and progression, while TBX19 and CDK2 were associated with NFPA recurrence.

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“…Similar results were as follows. NR2C2 regulated EZH2 through binding to its 5′UTR and promoted invasiveness of bladder cancer 42 . NR2C2 was upregulated in non-small cell lung cancer and was associated with poor prognosis of patients 43 , 44 .…”

Section: Discussionmentioning

confidence: 99%

NR2C2-uORF targeting UCA1-miR-627-5p-NR2C2 feedback loop to regulate the malignant behaviors of glioma cells

et al. 2018

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Accumulating evidence has highlighted the potential role of non-coding RNAs (ncRNAs) and upstream open-reading frames (uORFs) in the biological behaviors of glioblastoma. Here, we elucidated the function and possible molecular mechanisms of the effect of some ncRNAs and NR2C2-uORF on the biological behaviors of gliomas. Quantitative real-time PCR was conducted to profile the cell expression of lnc-UCA1 and microRNA-627-5p (miR-627-5p) in glioma tissues and cells. Western blot assay was used to determine the expression levels of NR2C2, SPOCK1, and NR2C2-uORF in glioma tissues and cells. Stable knockdown of lnc-UCA1 or overexpression of miR-627-5p in glioma cell lines (U87 and U251) were established to explore the function of lnc-UCA1 and miR-627-5p in glioma cells. Further, Dual luciferase report assay was used to investigate the correlation between lnc-UCA1 and miR-627-5p. Cell Counting Kit-8, transwell assays, and flow cytometry were used to investigate lnc-UCA1 and miR-627-5p function including cell proliferation, migration and invasion, and apoptosis, respectively. ChIP assays were used to ascertain the correlations between NR2C2 and SPOCK1 as well as NR2C2 between lnc-UCA1. This study confirmed that lnc-UCA1 was up-regulated in glioma tissues and cells. UCA1 knockdown inhibited the malignancies of glioma cells by reducing proliferation, migration, and invasion, but inducing apoptosis. We found that lnc-UCA1 acted as miR-627-5p sponge in a sequence-specific manner. Meanwhile, upregulated lnc-UCA1 inhibited miR-627-5p expression. In addition, miR-627-5p targeted 3′UTR of NR2C2 and down-regulated its expression. Moreover, UCA1 knockdown impaired NR2C2 expression by upregulating miR-627-5p. An uORF was identified in mRNA 5'UTR of NR2C2 and overexpression of whom negatively regulated NR2C2 expression. Remarkably, lnc-UCA1 knockdown combined with uORF overepression and NR2C2 knockdown led to severe tumor suppression in vivo. This study demonstrated that the NR2C2-uORF impaired the pivotal roles that UCA1-miR-627-5p-NR2C2 feedback loop had in regulating the malignancies of glioma cells by targeting NR2C2 directly. And this may provide a potential therapeutic strategy for treating glioma.

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TR4 Nuclear Receptor Alters the Prostate Cancer CD133+ Stem/Progenitor Cell Invasion via Modulating the EZH2-Related Metastasis Gene Expression

Cited by 16 publications

References 49 publications

TR4 Nuclear Receptor Different Roles in Prostate Cancer Progression

TR4 Nuclear Receptor Different Roles in Prostate Cancer Progression

Immunohistochemical Study of NR2C2, BTG2, TBX19, and CDK2 Expression in 31 Paired Primary/Recurrent Nonfunctioning Pituitary Adenomas

NR2C2-uORF targeting UCA1-miR-627-5p-NR2C2 feedback loop to regulate the malignant behaviors of glioma cells

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