TR2 and TR4 Orphan Nuclear Receptors

Lin, Shin-Jen; Yang, Dian; Yang, Guosheng; Lin, Chien-Chou; Chang, Hong-Chiang; Li, Gonghui; Chang, Chawnshang

doi:10.1016/bs.ctdb.2017.02.002

Cited by 28 publications

(21 citation statements)

References 58 publications

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“…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 . Silencing NR2C2 increased the resistance of hepatoma cells to cisplatin chemotherapy 45 .…”

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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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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“…JAZF1 has been reported to maintain glucose homeostasis through modulation of TR4 function. For instance, TR4 is known to bind to the promoter of phosphoenolpyruvate carboxykinase (PEPCK) and enhance its expression . Inhibition of TR4 by JAZF1 could markedly decrease PEPCK mRNA expression, leading to decreased hepatic glucose production …”

Section: Jazf1 In Metabolic Signalling Pathwaysmentioning

confidence: 99%

JAZF1, a relevant metabolic regulator in type 2 diabetes

Liao

Wang

et al. 2019

Diabetes Metabolism Res

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Excessive adiposity and metabolic inflammation are the key risk factors of type 2 diabetes mellitus (T2DM). Juxtaposed with another zinc finger gene 1 (JAZF1) has been identified as a novel transcriptional cofactor, with function of regulating glucose and lipid homeostasis and inflammation. JAZF1 is involved in metabolic process of T2DM via interaction with several nuclear receptors and protein kinases. Additionally, increasing evidence from genome-wide association studies (GWAS) has shown that JAZF1 polymorphisms are closely associated with T2DM. In this review, we have updated the latest research advances on JAZF1 and discussed its regulatory network in T2DM. The association between JAZF1 polymorphisms and T2DM is discussed as well. The information provided is of importance for guiding future studies as well as for the design of JAZF1-based T2DM therapy.

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“…Inhibition of ACACA can lead to either decreased cell proliferation (Jones et al, 2017;Singh, Yadav, Kumar, & Saini, 2015) or decreased apoptosis (Keenan et al, 2015) and increased risk of metastasis/tumor recurrence (in mice) (Rios Garcia et al, 2017). NR2C2 can inhibit cancer initiation, but promote cancer progression (Lin et al, 2017). In colon cancer cell lines, NR2C2 is required for cell survival and its inhibition induces cell death (McNew et al, 2016;Singh et al, 2012).…”

Section: F I G U R E 4 Autosomal Recessive Genes Analysismentioning

confidence: 99%

Exome sequencing in 51 early onset non‐familial CRC cases

Thutkawkorapin

Lindblom

Tham

2019

Molec Gen & Gen Med

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Background Colorectal cancer ( CRC ) cases with an age of onset <40 years suggests a germline genetic cause. In total, 51 simplex cases were included to test the hypothesis of CRC as a mendelian trait caused by either heterozygous autosomal dominant or bi‐allelic autosomal recessive pathogenic variants. Methods The cohort was whole exome sequenced ( WES ) at 100× coverage. Both a dominant‐ and recessive model were used for searching predisposing genetic factors. In addition, we assayed recessive variants of potential moderate risk that were enriched in our young‐onset CRC cohort. Variants were filtered using a candidate cancer gene list or by selecting variants more likely to be pathogenic based on variant type (e.g., loss‐of‐function) or allele frequency. Results We identified one pathogenic variant in PTEN in a patient subsequently confirmed to have a hereditary hamartoma tumor syndrome (Cowden syndrome) and one patient with a pathogenic heterozygous variant in PMS 2 that was originally not identified by WES due to low quality reads resulting from pseudogenes. In addition, we identified three heterozygous candidate missense variants in known cancer susceptibility genes ( BMPR 1A , BRIP 1 , and SRC ) , three truncating variants in possibly novel cancer genes ( CLSPN , SEC 24B , SSH 2 ) and four candidate missense variants in ACACA , NR 2C2 , INPP 4A, and DIDO 1 . We also identify five possible autosomal recessive candidate genes: ATP 10B , PKHD 1 , UGGT 2 , MYH 13 , TFF 3 . Conclusion Two clear pathogenic variants were identified in patients that had not been identified clinically. Thus, the chance of detecting a hereditary cancer syndrome in patients with CRC at young age but without family history is 2/51 (4%) and therefore the clinical benefit of genetic testing in this patient group is low. Of note, using stringent filtering, we have identified a total of ten candidate heterozygous variants and five possibly biallelic autosomal recessive candidate genes that warrant further study.

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TR2 and TR4 Orphan Nuclear Receptors

Cited by 28 publications

References 58 publications

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

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

JAZF1, a relevant metabolic regulator in type 2 diabetes

Exome sequencing in 51 early onset non‐familial CRC cases

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