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TPTEP1 通过 miR-1343-3p/SIRT3 轴抑制三阴性乳腺癌中脂肪酸代谢的重编程。

TPTEP1 impedes the reprogramming of fatty acid metabolism in triple negative breast cancer via miR-1343-3p/SIRT3 axis.

机构信息

Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150081, Heilongjiang Province, China.

Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150081, Heilongjiang Province, China.

出版信息

Int J Biol Macromol. 2024 Nov;280(Pt 2):135792. doi: 10.1016/j.ijbiomac.2024.135792. Epub 2024 Sep 19.

Abstract

Recently, the important role of fatty acid (FA) metabolism in cancers has been highlighted. Sirtuin 3 (SIRT3) is determined as an important regulator in the FA metabolism of cancer cells. We are going to verify whether and how lncRNA transmembrane phosphatase with tensin homology pseudogene 1 (TPTEP1) and SIRT3 may exert certain impact on the FA metabolism in triple-negative breast cancer (TNBC). Firstly, TPTEP1 was verified to be with low expression in TNBC cells. Moreover, down-regulation of TPTEP1 was caused by YY1 transcription factor. Functional assays determined the effects of TPTEP1 on the process of TNBC. The results disclosed that TPTEP1 up-regulation significantly repressed cell proliferation, migration, invasion, EMT and the reprogramming of FA metabolism in TNBC. Mechanism experiments detected the regulatory mechanism between TPTEP1 and SIRT3, which turned out that TPTEP1 positively regulated SIRT3 to affect FOXO3a and inhibit the Wnt/β-catenin pathway via sponging miR-1343-3p. All in all, TPTEP1 functioned as a tumor suppressor to regulate TNBC progression via the miR-1343-3p/SIRT3/FOXO3a/Wnt/β-catenin signaling.

摘要

最近,脂肪酸(FA)代谢在癌症中的重要作用得到了强调。Sirtuin 3(SIRT3)被确定为癌细胞 FA 代谢的重要调节剂。我们将验证 lncRNA 跨膜磷酸酶与张力蛋白同源假基因 1(TPTEP1)和 SIRT3 是否以及如何对三阴性乳腺癌(TNBC)中的 FA 代谢产生一定的影响。首先,验证了 TPTEP1 在 TNBC 细胞中表达水平较低。此外,YY1 转录因子导致 TPTEP1 下调。功能测定确定了 TPTEP1 对 TNBC 过程的影响。结果表明,TPTEP1 的上调显著抑制了 TNBC 细胞的增殖、迁移、侵袭、EMT 和 FA 代谢的重编程。机制实验检测了 TPTEP1 和 SIRT3 之间的调节机制,结果表明 TPTEP1 通过海绵 miR-1343-3p 正向调节 SIRT3 来影响 FOXO3a 并抑制 Wnt/β-catenin 通路。总之,TPTEP1 通过 miR-1343-3p/SIRT3/FOXO3a/Wnt/β-catenin 信号通路作为肿瘤抑制因子发挥作用,调节 TNBC 的进展。

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