卵巢癌症中单羧酸转运蛋白的系统分析及可能的治疗干预措施。

Channels (Austin, Tex.) Pub Date : 2023-12-01 Epub Date: 2023-11-07 DOI:10.1080/19336950.2023.2273008
Priti Chatterjee, Debaleena Bhowmik, Sib Sankar Roy
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摘要

单羧酸转运蛋白(MCTs)通过调节包括丙酮酸盐和乳酸盐在内的不同重要单羧酸盐的浓度依赖性转运,在代谢活性实体瘤中发挥着巨大作用,并由SLC16A基因家族编码。鉴于这些转运蛋白在肿瘤发生中发挥着广泛的功能,我们的目标是通过利用各种公开的数据库和网络资源,研究MCT1(SLC16A1)、MCT2(SLC16A 7)、MCT3(SLC16 A8)和MCT4(SLC16C3)与癌症上皮癌(EOC)病理生理学的关系。通过在EOC细胞系SKOV3和OAW-42中的体外实验,很少有计算机模拟结果得到证实。发现与正常人相比,OC组织中MCT1和MCT4在mRNA水平上调。然而,只有较高水平的MCT4 mRNA被发现与患者生存率低有关。MCT4与负责侵袭、迁移和免疫修饰的基因家族呈正相关,证明它是治疗干预中最重要的MCTs之一。我们比较了MCT1/2阻断剂SR13800和广谱MCT阻断剂α-氰基羟基肉桂酸(α-CHA)的作用,发现α-CHA在减少癌症细胞侵袭行为方面比MCT1/2拮抗剂SR1380具有更大的作用。根据我们的研究,MCT4已成为预测不良患者预后的前瞻性标志物和潜在的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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A systemic analysis of monocarboxylate transporters in ovarian cancer and possible therapeutic interventions.

Monocarboxylate transporters (MCTs) play an immense role in metabolically active solid tumors by regulating concentration-dependent transport of different important monocarboxylates including pyruvate and lactate and are encoded by the SLC16A family of genes. Given the vast array of functions, these transporters play in oncogenesis, our objective was to look into the association of MCT1 (SLC16A1), MCT2 (SLC16A7), MCT3 (SLC16A8), and MCT4 (SLC16A3) with Epithelial ovarian cancer (EOC) pathophysiology by exploiting various publicly available databases and web resources. Few of the in silico findings were confirmed via in vitro experiments in EOC cell lines, SKOV3 and OAW-42. MCT1 and MCT4 were found to be upregulated at the mRNA level in OC tissues compared to normal. However, only higher level of MCT4 mRNA was found to be associated with poor patient survival. MCT4 was positively correlated with gene families responsible for invasion, migration, and immune modification, proving it to be one of the most important MCTs for therapeutic intervention. We compared the effects of MCT1/2 blocker SR13800 and a broad-spectrum MCT blocker α-Cyano Hydroxy Cinnamic Acid (α-CHCA) and discovered that α-CHCA has a greater effect on diminishing the invasive behavior of the cancer cells than MCT1/2 blocker SR13800. From our study, MCT4 has emerged as a prospective marker for predicting poor patient outcomes and a potential therapeutic target.

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