Vitamin D-metabolizing enzyme CYP24A1 affects oncogenic behaviors of oral squamous cell carcinoma and its prognostic implication.

IF 1.2 4区医学 Q3 PATHOLOGY Medical Molecular Morphology Pub Date : 2024-09-01 Epub Date: 2024-05-21 DOI:10.1007/s00795-024-00387-y

Yuna Nakamori, Akira Takasawa, Kumi Takasawa, Daisuke Kyuno, Yusuke Ono, Kazufumi Magara, Naoya Nakahashi, Shohei Sekiguchi, Kei Tsuchihashi, Akihiro Miyazaki, Makoto Osanai

{"title":"Vitamin D-metabolizing enzyme CYP24A1 affects oncogenic behaviors of oral squamous cell carcinoma and its prognostic implication.","authors":"Yuna Nakamori, Akira Takasawa, Kumi Takasawa, Daisuke Kyuno, Yusuke Ono, Kazufumi Magara, Naoya Nakahashi, Shohei Sekiguchi, Kei Tsuchihashi, Akihiro Miyazaki, Makoto Osanai","doi":"10.1007/s00795-024-00387-y","DOIUrl":null,"url":null,"abstract":"<p><p>Vitamin D is an essential molecule for cellular homeostasis, playing a critical role in cell fate decisions including cell proliferation, differentiation, and viability. Accumulating evidence has revealed that expression of the vitamin D-metabolizing enzyme CYP24A1 is dysregulated in different types of human malignancy. CYP24A1 has been shown to be involved in the oncogenic property of a variety of carcinoma cells. However, the pathological relevance of CYP24A1 expression level in human oral malignancy remains to be clarified. In the present study, suppression of CYP24A1 expression in oral squamous cell carcinoma (OSCC) cells increased cell proliferation, invasive activity, colony formation efficacy, and tumor growth in vivo. In addition, knockout of CYP24A1 expression inhibited cell death induced by two different types of anticancer drugs, i.e., fluorouracil and cisplatin. Gene clustering by RNA-sequence analysis revealed that several signaling molecules associated with MYC are involved in CYP24A1-mediated oncogenic behaviors. Furthermore, decreased expression level of CYP24A1 was observed in 124/204 cases (61%) of OSCC and was shown to be associated with short relapse-free and overall survival periods. The results showed that a low expression level of CYP24A1 promotes the oncogenic activity of OSCC and is significantly associated with poor prognosis in patients with this malignancy.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"185-199"},"PeriodicalIF":1.2000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medical Molecular Morphology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00795-024-00387-y","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/21 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PATHOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Vitamin D is an essential molecule for cellular homeostasis, playing a critical role in cell fate decisions including cell proliferation, differentiation, and viability. Accumulating evidence has revealed that expression of the vitamin D-metabolizing enzyme CYP24A1 is dysregulated in different types of human malignancy. CYP24A1 has been shown to be involved in the oncogenic property of a variety of carcinoma cells. However, the pathological relevance of CYP24A1 expression level in human oral malignancy remains to be clarified. In the present study, suppression of CYP24A1 expression in oral squamous cell carcinoma (OSCC) cells increased cell proliferation, invasive activity, colony formation efficacy, and tumor growth in vivo. In addition, knockout of CYP24A1 expression inhibited cell death induced by two different types of anticancer drugs, i.e., fluorouracil and cisplatin. Gene clustering by RNA-sequence analysis revealed that several signaling molecules associated with MYC are involved in CYP24A1-mediated oncogenic behaviors. Furthermore, decreased expression level of CYP24A1 was observed in 124/204 cases (61%) of OSCC and was shown to be associated with short relapse-free and overall survival periods. The results showed that a low expression level of CYP24A1 promotes the oncogenic activity of OSCC and is significantly associated with poor prognosis in patients with this malignancy.

Abstract Image

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

维生素 D 代谢酶 CYP24A1 对口腔鳞状细胞癌致癌行为的影响及其预后意义

维生素 D 是细胞稳态的重要分子，在细胞增殖、分化和存活等细胞命运决定中发挥着关键作用。越来越多的证据表明，维生素 D 代谢酶 CYP24A1 在不同类型的人类恶性肿瘤中表达失调。研究表明，CYP24A1 与多种癌细胞的致癌特性有关。然而，CYP24A1 表达水平在人类口腔恶性肿瘤中的病理相关性仍有待明确。在本研究中，抑制 CYP24A1 在口腔鳞状细胞癌（OSCC）细胞中的表达会增加细胞增殖、侵袭活性、集落形成效力和体内肿瘤生长。此外，CYP24A1表达的敲除抑制了两种不同类型抗癌药物（即氟尿嘧啶和顺铂）诱导的细胞死亡。通过 RNA 序列分析进行基因聚类发现，与 MYC 相关的几个信号分子参与了 CYP24A1 介导的致癌行为。此外，在124/204例（61%）OSCC病例中观察到CYP24A1表达水平降低，并显示这与无复发和总生存期短有关。研究结果表明，CYP24A1的低表达水平促进了OSCC的致癌活性，并与该恶性肿瘤患者的不良预后显著相关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Medical Molecular Morphology 医学-病理学

CiteScore

2.90

自引率

5.60%

发文量

审稿时长

>12 weeks

期刊介绍： Medical Molecular Morphology is an international forum for researchers in both basic and clinical medicine to present and discuss new research on the structural mechanisms and the processes of health and disease at the molecular level. The structures of molecules, organelles, cells, tissues, and organs determine their normal function. Disease is thus best understood in terms of structural changes in these different levels of biological organization, especially in molecules and molecular interactions as well as the cellular localization of chemical components. Medical Molecular Morphology welcomes articles on basic or clinical research in the fields of cell biology, molecular biology, and medical, veterinary, and dental sciences using techniques for structural research such as electron microscopy, confocal laser scanning microscopy, enzyme histochemistry, immunohistochemistry, radioautography, X-ray microanalysis, and in situ hybridization. Manuscripts submitted for publication must contain a statement to the effect that all human studies have been reviewed by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in an appropriate version of the 1964 Declaration of Helsinki. It should also be stated clearly in the text that all persons gave their informed consent prior to their inclusion in the study. Details that might disclose the identity of the subjects under study should be omitted.