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分析孤儿核受体NR4A1、NR4A2和NR4A3在子宫颈癌前病变和宫颈炎中的基因表达谱。

Analysing the gene expression profiles of the orphan nuclear receptors NR4A1, NR4A2 and NR4A3 in premalignant lesions of the cervix and cervicitis.

作者信息

Cruz-Nieves Rosa P, Ramírez-Rosales Gladys E, González-Ramírez Javier, Sánchez-Muñoz Fausto, Ruiz-Hernández Armando

机构信息

Department of Pharmacology, School of Medicine, Autonomous University of Baja California, Mexicali, Baja California, Mexico.

Department of Pathophysiology, School of Medicine, Autonomous University of Baja California, Mexicali, Baja California, Mexico.

出版信息

Eur J Obstet Gynecol Reprod Biol X. 2024 Nov 13;24:100355. doi: 10.1016/j.eurox.2024.100355. eCollection 2024 Dec.

DOI:10.1016/j.eurox.2024.100355
PMID:39639963
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11617305/
Abstract

OBJECTIVE

The main objective of the present study was to evaluate the expression of nuclear orphan receptors in the development of Uterine Cervical Cancer (UCC). The principal cause of dysplastic changes in cervical epithelium is the presence of the human papilloma virus leading to the development of cervical intraepithelial neoplasia I (CIN I), high-grade lesions (CIN II and CIN III) and, finally, invasive cancer. Despite the existence of various treatments and vaccines, there is still a high mortality rate. There is evidence of the participation of a group of nuclear receptors called orphans in the development of various diseases, including cancer.

STUDY DESIGN

The expression levels of the orphan receptors NR4A1, NR4A2, and NR4A3 were measured using real-time polymerase chain reaction (RT-PCR) in samples obtained through colposcopy from forty-five patients who attended the Medical Oncology Specialties Unit (UNEME) in Mexicali, B.C.

RESULTS

Forty-five cervical biopsy results were obtained, indicating cervicitis, CIN I, or CIN III, none of them CIN II. Our results showed that orphan receptors expressed in a specific manner depending on the degree of premalignant lesions. NR4A1 overexpressed in cervicitis (p < 0.05). NR4A3 was significantly expressed in CIN I (p < 0.05) and NR4A2 was expressed in both cervicitis and CIN III (p > 0.05).

CONCLUSION

Our data suggest, for the first time, that nuclear receptors might be involved in the various stages that precede the development of invasive UCC.

摘要

目的

本研究的主要目的是评估核孤儿受体在子宫颈癌(UCC)发展过程中的表达。宫颈上皮发育异常变化的主要原因是人类乳头瘤病毒的存在,这会导致宫颈上皮内瘤变I级(CIN I)、高级别病变(CIN II和CIN III),最终发展为浸润性癌。尽管存在各种治疗方法和疫苗,但死亡率仍然很高。有证据表明,一组称为孤儿的核受体参与了包括癌症在内的各种疾病的发展。

研究设计

使用实时聚合酶链反应(RT-PCR)测量了从墨西哥下加利福尼亚州墨西卡利市医学肿瘤专科单位(UNEME)就诊的45名患者通过阴道镜检查获得的样本中孤儿受体NR4A1、NR4A2和NR4A3的表达水平。

结果

获得了45份宫颈活检结果,表明为宫颈炎、CIN I或CIN III,其中没有CIN II。我们的结果表明,孤儿受体根据癌前病变的程度以特定方式表达。NR4A1在宫颈炎中过表达(p < 0.05)。NR4A3在CIN I中显著表达(p < 0.05),而NR4A2在宫颈炎和CIN III中均有表达(p > 0.05)。

结论

我们的数据首次表明,核受体可能参与了浸润性UCC发展之前的各个阶段。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3779/11617305/783787f44f17/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3779/11617305/8167fa443f4d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3779/11617305/163c789a02f6/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3779/11617305/783787f44f17/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3779/11617305/8167fa443f4d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3779/11617305/163c789a02f6/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3779/11617305/783787f44f17/gr3.jpg

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Importance of the Immune Microenvironment in the Spontaneous Regression of Cervical Squamous Intraepithelial Lesions (cSIL) and Implications for Immunotherapy.
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NR4A nuclear receptors in T and B lymphocytes: Gatekeepers of immune tolerance.NR4A 核受体在 T 和 B 淋巴细胞中的作用:免疫耐受的守门员。
Immunol Rev. 2022 May;307(1):116-133. doi: 10.1111/imr.13072. Epub 2022 Feb 17.
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