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International Ophthalmology

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Open Access 01-12-2024 | Retinoblastoma | Original Paper

Low expression of NR1D1 and NR2E3 is associated with advanced features of retinoblastoma

Authors: Jie Ding, Jie Sun, Rui-Qi Ma, Ke Zheng, Yi-Nan Han

Published in: International Ophthalmology | Issue 1/2024

Abstract

Purpose

To investigate the expression of nuclear receptor subfamily 1 group D member 1 (NR1D1) and nuclear receptor subfamily 2 group E Member 3 (NR2E3) in retinoblastoma (RB) and their correlation with the clinical and pathological features of RB.

Methods

Immunohistochemical (IHC) assays were performed to detect and evaluate the expression levels of NR1D1 and NR2E3 in paraffin-embedded tissue samples. The relationship between the expression levels and clinicopathological characteristics of RB patients was analyzed using the χ² test or Fisher exact test.

Results

A total of 51 RB patients were involved in this research. The expression levels of NR1D1 (P = 0.004) and NR2E3 (P = 0.024) were significantly lower in RB tumor tissues than in normal retina. The expression levels of NR1D1 and NR2E3 were less positive in RB patients with advanced stages (P = 0.007, P = 0.015), choroidal infiltration (P = 0.003, P = 0.029), and optic nerve infiltration (P = 0.036, P = 0.003). In addition, a low expression level of NR2E3 was associated with high-risk pathology (P = 0.025) and necrosis (P = 0.035) of RB tissues.

Conclusion

The expression levels of NR1D1 and NR2E3 were decreased in RB and closely associated with the clinical stage and high invasion of the disease. These findings provide new insights into the mechanism of RB progression and suggest that NR1D1 and NR2E3 could be potential targets for treatment strategies.

Villegas VM, Hess DJ, Wildner A, Gold AS, Murray TG (2013) Retinoblastoma. Curr Opin Ophthalmol 24(6):581–588CrossRefPubMed

Chen YH, Lin HY, Hsu WM, Lee SM, Cheng CY (2010) Retinoblastoma in Taiwan: incidence and survival characteristics from 1979 to 2003. Eye (Lond) 24(2):318–322CrossRefPubMed

Kaewkhaw R, Rojanaporn D (2020) Retinoblastoma: etiology, modeling, and treatment. Cancers 12(8):2304CrossRefPubMedPubMedCentral

Wu D, Cheung A, Wang Y, Yu S, Chan FL (2016) The emerging roles of orphan nuclear receptors in prostate cancer. Biochim Biophys Acta 1866(1):23–36PubMed

Na H, Han J, Ka N-L, Lee M-H, Choi Y-L, Shin YK et al (2019) High expression of NR1D1 is associated with good prognosis in triple-negative breast cancer patients treated with chemotherapy. Breast Cancer Research : BCR 21(1):127CrossRefPubMedPubMedCentral

Wang H, Fu Y (2021) NR1D1 suppressed the growth of ovarian cancer by abrogating the JAK/STAT3 signaling pathway. BMC Cancer 21(1):871CrossRefPubMedPubMedCentral

Park Y-Y, Kim K, Kim S-B, Hennessy BT, Kim SM, Park ES et al (2012) Reconstruction of nuclear receptor network reveals that NR2E3 is a novel upstream regulator of ESR1 in breast cancer. EMBO Mol Med 4(1):52–67CrossRefPubMedPubMedCentral

Khanal T, Choi K, Leung Y-K, Wang J, Kim D, Janakiram V et al (2017) Loss of NR2E3 represses AHR by LSD1 reprogramming, is associated with poor prognosis in liver cancer. Sci Rep 7(1):10662ADSCrossRefPubMedPubMedCentral

Shields CL, Mashayekhi A, Au AK, Czyz C, Leahey A, Meadows AT et al (2006) The international classification of retinoblastoma predicts chemoreduction success. Ophthalmology 113(12):2276–2280CrossRefPubMed

10.

Tomar AS, Finger PT, Gallie B, Kivelä TT, Mallipatna A, Zhang C et al (2022) High-risk pathologic features based on presenting findings in advanced intraocular retinoblastoma: a multicenter, international data-sharing american joint committee on cancer study. Ophthalmology 129(8):923–932CrossRefPubMed

11.

Wang HF, Zheng SF, Chen Y, Zhou ZY, Xu J (2018) Correlations between claudin-1 and PIGF expressions in retinoblastoma. Eur Rev Med Pharmacol Sci 22(13):4196–4203PubMed

12.

Liu J, Ottaviani D, Sefta M, Desbrousses C, Chapeaublanc E, Aschero R et al (2021) A high-risk retinoblastoma subtype with stemness features, dedifferentiated cone states and neuronal/ganglion cell gene expression. Nat Commun 12(1):5578ADSCrossRefPubMedPubMedCentral

13.

Wang X, Wang N, Wei X, Yu H, Wang Z (2018) REV-ERBα reduction is associated with clinicopathological features and prognosis in human gastric cancer. Oncol Lett 16(2):1499–1506PubMedPubMedCentral

14.

Wang Y, Kojetin D, Burris TP (2015) Anti-proliferative actions of a synthetic REV-ERBα/β agonist in breast cancer cells. Biochem Pharmacol 96(4):315–322CrossRefPubMedPubMedCentral

15.

Sulli G, Rommel A, Wang X, Kolar MJ, Puca F, Saghatelian A et al (2018) Pharmacological activation of REV-ERBs is lethal in cancer and oncogene-induced senescence. Nature 553(7688):351–355ADSCrossRefPubMedPubMedCentral

16.

Aísa-Marín I, López-Iniesta MJ, Milla S, Lillo J, Navarro G, de la Villa P et al (2020) Nr2e3 functional domain ablation by CRISPR-Cas9D10A identifies a new isoform and generates retinitis pigmentosa and enhanced S-cone syndrome models. Neurobiol Dis 146:105122CrossRefPubMed

17.

Mollema NJ, Yuan Y, Jelcick AS, Sachs AJ, von Alpen D, Schorderet D et al (2011) Nuclear receptor Rev-erb alpha (Nr1d1) functions in concert with Nr2e3 to regulate transcriptional networks in the retina. PLoS ONE 6(3):e17494ADSCrossRefPubMedPubMedCentral

18.

Kapatai G, Brundler MA, Jenkinson H, Kearns P, Parulekar M, Peet AC et al (2013) Gene expression profiling identifies different sub-types of retinoblastoma. Br J Cancer 109(2):512–525CrossRefPubMedPubMedCentral

Title: Low expression of NR1D1 and NR2E3 is associated with advanced features of retinoblastoma
Authors: Jie Ding
Jie Sun
Rui-Qi Ma
Ke Zheng
Yi-Nan Han
Publication date: 01-12-2024
Publisher: Springer Netherlands
Keywords: Retinoblastoma
Retinoblastoma
Pathology
Published in: International Ophthalmology / Issue 1/2024
Print ISSN: 0165-5701
Electronic ISSN: 1573-2630
DOI: https://doi.org/10.1007/s10792-024-03055-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Low expression of NR1D1 and NR2E3 is associated with advanced features of retinoblastoma

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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