OMA1 and YME1L as a Diagnostic Panel in Hepatocellular Carcinoma.

IF 2.5 3区 工程技术 Q2 BIOLOGY Yale Journal of Biology and Medicine Pub Date : 2023-12-29 eCollection Date: 2023-12-01 DOI:10.59249/BWBY8971
Shimaa A Abass, Nabil Mohie Abdel-Hamid, Ahmed M Elshazly, Walied Abdo, Sherin Zakaria
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Abstract

Identifying new hepatocellular carcinoma (HCC)-driven signaling molecules and discovering their molecular mechanisms are crucial for efficient and better outcomes. Recently, OMA1 and YME1L, the inner mitochondrial proteases, were displayed to be associated with tumor progression in various cancers; however, their role in HCC has not yet been studied. Therefore, we evaluated the possible role of OMA1/YME1L in HCC staging and discussed their potential role in cellular apoptosis and proliferation. Our study was performed using four groups of male albino rats: a normal control and three diethyl nitrosamine-treated groups for 8, 16, and 24 weeks. The OMA1 and YME1L, matrix-metalloproteinase-9 (MMP-9), and cyclin D1 content were measured in liver tissues, while alpha-fetoprotein (AFP) level was assessed in serum. Additionally, Ki-67 expression was evaluated by immunohistochemistry. The relative hepatic expression of Bax, and tissue inhibitor matrix metalloproteinase (TIMP-3) was measured. Herein, we confirmed for the first time that OMA1 is down-regulated while YME1L is up-regulated in HCC in the three studied stages with subsequent inhibition of apoptosis and cell cycle progression. Furthermore, these proteases have a possible role in metastasis. These newly recognized results suggested OMA1 and YME1L as possible diagnostic tools and therapeutic targets for HCC management.

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将 OMA1 和 YME1L 作为肝细胞癌的诊断面板
确定新的肝细胞癌(HCC)信号传导分子并发现其分子机制对于有效和更好地治疗至关重要。最近,线粒体内部蛋白酶 OMA1 和 YME1L 被证实与多种癌症的肿瘤进展有关,但它们在 HCC 中的作用尚未得到研究。因此,我们评估了 OMA1/YME1L 在 HCC 分期中的可能作用,并讨论了它们在细胞凋亡和增殖中的潜在作用。我们的研究使用了四组雄性白化大鼠:一组正常对照组和三组二乙基亚硝胺处理组,处理时间分别为 8 周、16 周和 24 周。我们测量了肝组织中的 OMA1 和 YME1L、基质金属蛋白酶-9(MMP-9)和细胞周期蛋白 D1 的含量,同时评估了血清中甲胎蛋白(AFP)的水平。此外,还通过免疫组化评估了 Ki-67 的表达。还测量了 Bax 和组织抑制基质金属蛋白酶(TIMP-3)在肝脏中的相对表达。在此,我们首次证实,在所研究的三个阶段中,OMA1 在 HCC 中被下调,而 YME1L 则被上调,从而抑制了细胞凋亡和细胞周期的进展。此外,这些蛋白酶还可能在转移中发挥作用。这些新发现表明,OMA1 和 YME1L 可作为诊断工具和治疗 HCC 的靶点。
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来源期刊
Yale Journal of Biology and Medicine
Yale Journal of Biology and Medicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
5.00
自引率
0.00%
发文量
41
期刊介绍: The Yale Journal of Biology and Medicine (YJBM) is a graduate and medical student-run, peer-reviewed, open-access journal dedicated to the publication of original research articles, scientific reviews, articles on medical history, personal perspectives on medicine, policy analyses, case reports, and symposia related to biomedical matters. YJBM is published quarterly and aims to publish articles of interest to both physicians and scientists. YJBM is and has been an internationally distributed journal with a long history of landmark articles. Our contributors feature a notable list of philosophers, statesmen, scientists, and physicians, including Ernst Cassirer, Harvey Cushing, Rene Dubos, Edward Kennedy, Donald Seldin, and Jack Strominger. Our Editorial Board consists of students and faculty members from Yale School of Medicine and Yale University Graduate School of Arts & Sciences. All manuscripts submitted to YJBM are first evaluated on the basis of scientific quality, originality, appropriateness, contribution to the field, and style. Suitable manuscripts are then subject to rigorous, fair, and rapid peer review.
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