异柠檬酸脱氢酶 3A 是 TCA 循环的限速酶，可通过调节 MTA1（NuRD 复合物的核心成分）促进肝细胞癌迁移和侵袭。,American journal of cancer research

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异柠檬酸脱氢酶 3A 是 TCA 循环的限速酶，可通过调节 MTA1（NuRD 复合物的核心成分）促进肝细胞癌迁移和侵袭。
American journal of cancer research Pub Date : 2020-10-01
Xujun Liu ₁ , Yan Qiao ₁ , Xia Ting ₁ , Wenzhe Si ₁

Affiliation

肝细胞癌 (HCC) 的精确分子机制仍然不明确。异柠檬酸脱氢酶 3A (IDH3A) 被称为 IDH3 异四聚体的亚基。据我们所知，IDH3A 在恶性肿瘤中的生物学效应尚不清楚。在这里，我们报告了 IDH3A 在 HCC 组织中显着上调；此外，IDH3A 的高表达与肿瘤大小和 HCC 的临床病理分期密切相关。RNA-seq 显示 IDH3A 的缺失会影响转移相关基因 1 (MTA1) 的表达，MTA1 是一种致癌基因，与多种癌症类型向转移阶段的进展有关。细胞转染用于上调和下调 HCC 细胞中 IDH3A 的表达。使用伤口愈合试验评估 HCC 细胞的迁移活性。同时进行transwell测定以检测HCC细胞的侵袭。RNA-seq、RT-qPCR 和蛋白质印迹被用来验证 MTA1 作为潜在的靶基因。本研究表明，IDH3A 可以通过诱导 MTA1 表达上调 MTA1 表达并促进 HCC 上皮间质转化 (EMT)，从而促进细胞迁移和 HCC 细胞的侵袭。在这里，我们证明了 IDH3A 在 HCC 进展中的重要性。IDH3A 轴的鉴定为 HCC 的发病机制提供了新的见解，IDH3A 轴可能代表了治疗 HCC 的新靶点。本研究表明，IDH3A 可以通过诱导 MTA1 表达上调 MTA1 表达并促进 HCC 上皮间质转化 (EMT)，从而促进细胞迁移和 HCC 细胞的侵袭。在这里，我们证明了 IDH3A 在 HCC 进展中的重要性。IDH3A 轴的鉴定为 HCC 的发病机制提供了新的见解，IDH3A 轴可能代表了治疗 HCC 的新靶点。本研究表明，IDH3A 可以通过诱导 MTA1 表达上调 MTA1 表达并促进 HCC 上皮间质转化 (EMT)，从而促进细胞迁移和 HCC 细胞的侵袭。在这里，我们证明了 IDH3A 在 HCC 进展中的重要性。IDH3A 轴的鉴定为 HCC 的发病机制提供了新的见解，IDH3A 轴可能代表了治疗 HCC 的新靶点。

"点击查看英文标题和摘要"

Isocitrate dehydrogenase 3A, a rate-limiting enzyme of the TCA cycle, promotes hepatocellular carcinoma migration and invasion through regulation of MTA1, a core component of the NuRD complex.

The precise molecular mechanism of hepatocellular carcinoma (HCC) remains ambiguous. Isocitrate dehydrogenase 3A (IDH3A) is known as a subunit of the IDH3 heterotetramer. To the best of our knowledge, the biological effect of IDH3A in malignant tumors is unclear. Here, we report that IDH3A is significantly upregulated in HCC tissues; moreover, high expression of IDH3A is strongly associated with tumor size and the clinicopathologic stage of HCC. RNA-seq revealed that depletion of IDH3A affects the expression of metastasis associated 1 (MTA1), an oncogene which is related to the progression of numerous cancer types to the metastasis stage. Cell transfection was used to upregulate and downregulate the expression of IDH3A in HCC cells. The migration activity of HCC cells was assessed using wound healing assays. While transwell assays were carried out to detect the invasion of HCC cells. RNA-seq, RT-qPCR and western blot were used to validate MTA1 as a potential target gene. The present study suggested that IDH3A can upregulate MTA1 expression and promote epithelial-mesenchymal transition (EMT) in HCC by inducing MTA1 expression, thereby facilitating cell migration and invasion of HCC cells. Here, we demonstrated the importance of IDH3A in HCC progression. The identification of the IDH3A axis provides novel insight into the pathogenesis of HCC, and the IDH3A axis might represent a novel target for the treatment of HCC.

更新日期：2020-10-01

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