PGRMC1和PAQR4是一种罕见亚型卵巢癌很有希望的分子靶点。

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-10-26 eCollection Date: 2024-01-01 DOI:10.1515/biol-2022-0982
Kamila Kozłowska-Tomczyk, Norbert Borski, Paulina Głód, Justyna Gogola-Mruk, Anna Ptak
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引用次数: 0

摘要

卵巢癌(OC)的异质性给开发有效的治疗方法带来了困难。如今,激素疗法在卵巢癌的治疗中发挥着越来越重要的作用;然而,迄今为止,激素调节剂只取得了有限的成功。为了给不同亚型 OC 的激素治疗提供更严谨的依据,本研究采用了一系列生物信息学方法来分析编码膜孕酮(PGRMC1、孕激素和脂肪Q受体 [PAQR] 家族)和雄激素(锌转运体成员9 [ZIP9]、OXER1)受体的基因的表达谱。我们的研究还调查了它们在 OC 中的预后价值。我们发现 ZIP9 和 OXER1 的表达在不同 OC 亚型之间以及患者肿瘤和正常组织之间存在差异。编码 PAQR7 和 PAQR8 的 mRNA 在一组 OC 细胞系中的表达量低于 qPCR 检测限,并且在肿瘤组织样本中下调,而在罕见亚型的 OC 细胞系中则观察到 PGRMC1 和 PAQR4 mRNA 的高表达。此外,化学抑制 PGRMC1 可降低以 COV434 细胞为代表的罕见 OC 的存活率。总之,PGRMC1 和 PAQR4 是很有希望的抗癌治疗靶点,特别是对于罕见亚型 OC。这些发现可能反映了观察到的不同亚型 OC 对激素疗法反应的差异。
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PGRMC1 and PAQR4 are promising molecular targets for a rare subtype of ovarian cancer.

The heterogeneity of ovarian cancer (OC) has made developing effective treatments difficult. Nowadays, hormone therapy plays a growing role in the treatment of OC; however, hormone modulators have had only limited success so far. To provide a more rigorous foundation for hormonal therapy for different OC subtypes, the current study used a series of bioinformatics approaches to analyse the expression profiles of genes encoding membrane progesterone (PGRMC1, progestins and the adipoQ receptor [PAQR] family), and androgen (zinc transporter member 9 [ZIP9], OXER1) receptors. Our work investigated also their prognostic value in the context of OC. We found differences in expression of ZIP9 and OXER1 between different OC subtypes, as well as between patient tumour and normal tissues. Expression of mRNA encoding PAQR7 and PAQR8 in a panel of OC cell lines was below the qPCR detection limit and was downregulated in tumour tissue samples, whereas high expression of PGRMC1 and PAQR4 mRNA was observed in rare subtypes of OC cell lines. In addition, chemical inhibition of PGRMC1 reduced the viability of rare OCs represented by COV434 cells. In conclusion, PGRMC1 and PAQR4 are promising targets for anticancer therapy, particularly for rare subtypes of OC. These findings may reflect differences in the observed responses of various OC subtypes to hormone therapy.

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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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