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≤ 通过调节 HPV 介导的宫颈癌,细胞周期蛋白 D1 蛋白影响全球女性健康。

≤ Cyclin D1 protein affecting global women's health by regulating HPV mediated adenocarcinoma of the uterine cervix.

机构信息

Division of Molecular Genetics & Biochemistry, ICMR-National Institute of Cancer Prevention and Research (NICPR), Noida, India.

Division of Preventive Oncology, ICMR-National Institute of Cancer Prevention and Research (NICPR), Noida, India.

出版信息

Sci Rep. 2019 Mar 22;9(1):5019. doi: 10.1038/s41598-019-41394-9.

Abstract

Adenocarcinoma (ADC) of the uterine cervix (UC) is a rare form of cervical cancer (CC) caused due to the infection of Human Papilloma Virus (HPV). Cyclin D1 is one of the downstream targets of aberrantly activated Notch signaling, contribute to the etiology of CC. However, little is known about the role of Cyclin D1 in the modulation of cervical ADC and is controversial. The purpose of this study is to determine the role of Cyclin D1 protein and to elucidate the combined analysis with Notch signaling proteins in HPV associated ADCs of CC. A total of 60 biopsy samples (40 normal and 20 ADCs of CC) were analyzed for the expression of Cyclin D1 in HPV associated ADCs via immunohistochemistry and by immunoblotting. HPV-16 positive ADC patients showed a strong association with the Cyclin D1 expression (p = 0.007). The significant mean difference (p = 0.0001) and the pairwise comparison between Cyclin D1/JAG1 (p = 0.0001), and Cyclin D1/Notch-3 (p = 0.0001) were observed. The above Notch signaling proteins showed their synergistic role in modulating Cyclin D1 which in-turn regulates HPV-16 associated ADC of the uterine cervix (UC), affecting women's global health.

摘要

宫颈腺癌(ADC)是一种罕见的宫颈癌(CC)形式,由人乳头瘤病毒(HPV)感染引起。细胞周期蛋白 D1 是异常激活的 Notch 信号转导的下游靶标之一,有助于 CC 的发病机制。然而,关于细胞周期蛋白 D1 在调节宫颈 ADC 中的作用知之甚少,并且存在争议。本研究旨在确定细胞周期蛋白 D1 蛋白的作用,并阐明与 Notch 信号蛋白的联合分析在 HPV 相关 CC 的 ADC 中的作用。通过免疫组织化学和免疫印迹法分析了 60 个活检样本(40 个正常和 20 个 CC 的 ADC)中 HPV 相关 ADC 中细胞周期蛋白 D1 的表达。HPV-16 阳性 ADC 患者与细胞周期蛋白 D1 表达呈强相关(p=0.007)。观察到细胞周期蛋白 D1/JAG1(p=0.0001)和细胞周期蛋白 D1/Notch-3(p=0.0001)之间存在显著的平均差异(p=0.0001)和两两比较。上述 Notch 信号蛋白显示出协同作用,调节细胞周期蛋白 D1,进而调节 HPV-16 相关的宫颈腺癌(UC),影响全球妇女的健康。

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