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MITD1 缺乏通过 TAZ/SLC7A11 通路诱导铁死亡来抑制透明细胞肾细胞癌的生长和迁移。

MITD1 Deficiency Suppresses Clear Cell Renal Cell Carcinoma Growth and Migration by Inducing Ferroptosis through the TAZ/SLC7A11 Pathway.

机构信息

Department of Urology, Renmin Hospital of Wuhan University, Wuhan, 430060 Hubei, China.

出版信息

Oxid Med Cell Longev. 2022 Aug 22;2022:7560569. doi: 10.1155/2022/7560569. eCollection 2022.

Abstract

Clear cell renal cell carcinoma (ccRCC), the major histopathological subtype of renal cancer, is sensitive to ferroptosis. MIT-domain containing protein 1 (MITD1) has been reported to play an important role in hepatocellular carcinoma, while it remains unclear whether MITD1 is involved in ccRCC. Based on available data in The Cancer Genome Atlas, we found the expression of MITD1 increased through bioinformatics analysis and high MITD1 expression suggests a poor prognosis. And we validated that MITD1 expressed significantly in ccRCC through Western blot analysis. Then, we further compared the proliferation and migration capacity of ccRCC before and after MITD1 knockdown and further explored the effect of MITD1 knockdown on ferroptosis. The results indicated that MITD1 knockdown inhibited ccRCC cell proliferation and migration and induced ferroptosis in ccRCC. Furthermore, we found and analyzed the key molecule TAZ which was involved in ferroptosis caused by MITD1 knockdown. Subsequent overexpression experiments demonstrated that MITD1 knockdown induced ferroptosis and suppressed tumor growth and migration through the TAZ/SLC7A11 pathway. In summary, our study revealed the role of MITD1 in the ferroptosis of ccRCC and provided a novel target for ccRCC treatment.

摘要

透明细胞肾细胞癌 (ccRCC) 是肾癌的主要组织病理学亚型,对铁死亡敏感。MIT 结构域包含蛋白 1 (MITD1) 已被报道在肝细胞癌中发挥重要作用,而 MITD1 是否参与 ccRCC 尚不清楚。基于 The Cancer Genome Atlas 中的可用数据,我们通过生物信息学分析发现 MITD1 的表达增加,高表达 MITD1 提示预后不良。我们通过 Western blot 分析进一步验证了 MITD1 在 ccRCC 中的表达显著上调。然后,我们进一步比较了 MITD1 敲低前后 ccRCC 的增殖和迁移能力,并进一步探讨了 MITD1 敲低对铁死亡的影响。结果表明,MITD1 敲低抑制 ccRCC 细胞增殖和迁移,并诱导 ccRCC 发生铁死亡。此外,我们发现并分析了参与 MITD1 敲低诱导的铁死亡的关键分子 TAZ。随后的过表达实验表明,MITD1 敲低通过 TAZ/SLC7A11 通路诱导铁死亡,抑制肿瘤生长和迁移。综上所述,我们的研究揭示了 MITD1 在 ccRCC 铁死亡中的作用,并为 ccRCC 的治疗提供了新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae13/9423985/129eb5da96c1/OMCL2022-7560569.001.jpg

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