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长链非编码 RNA LINC00649 通过 NF90/NF45 复合物维持 HIF-1α 的稳定性,促进三阴性乳腺癌的生长和转移。

LncRNA LINC00649 promotes the growth and metastasis of triple-negative breast cancer by maintaining the stability of HIF-1α through the NF90/NF45 complex.

机构信息

Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Henan, China.

出版信息

Cell Cycle. 2022 May;21(10):1034-1047. doi: 10.1080/15384101.2022.2040283. Epub 2022 Feb 21.

Abstract

There is no clear treatment guideline or individualized treatment plan for triple-negative breast cancer (TNBC). The aim of this study was to investigate more effective targets for TNBC-targeted therapy. MDA-MB-231 and BT549 cell lines were used to explore the function of LINC00649 on the proliferation, invasion, and migration of TNBC cells. A mice subcutaneous tumor model and a pulmonary metastasis model was established to identify the role of LINC00649 on the growth and metastasis of TNBC . LINC00649 was found to be a key molecule involved in the occurrence and development of TNBC by screening of public databases and detection of TNBC clinical samples. LINC00649 increased hypoxia-inducible factor 1α (HIF-1α) mRNA stability and protein expression by interacting with the nuclear factor 90 (NF90)/NF45 complex. , interference with LINC00649 inhibits MDA-MB-231 and BT549 cell proliferation, migration, and invasion, and the addition of HIF-1α revised this effect. experiments showed that LINC00649 promoted the growth and metastasis of TNBC. We demonstrated that LINC00649 interacts with the NF90/NF45 complex to increase the mRNA stability of HIF-1α and up-regulate HIF-1α expression, thereby inducing the proliferation, invasion, and migration of TNBC cells as well as tumor growth and metastasis.

摘要

目前针对三阴性乳腺癌(TNBC)尚缺乏明确的治疗指南或个体化治疗方案。本研究旨在寻找更有效的 TNBC 靶向治疗靶点。我们使用 MDA-MB-231 和 BT549 细胞系探索 LINC00649 对 TNBC 细胞增殖、侵袭和迁移的功能。建立了小鼠皮下肿瘤模型和肺转移模型,以鉴定 LINC00649 对 TNBC 生长和转移的作用。通过公共数据库筛选和 TNBC 临床样本检测,发现 LINC00649 是参与 TNBC 发生发展的关键分子。LINC00649 通过与核因子 90(NF90)/NF45 复合物相互作用,增加缺氧诱导因子 1α(HIF-1α)mRNA 的稳定性和蛋白表达。干扰 LINC00649 抑制 MDA-MB-231 和 BT549 细胞的增殖、迁移和侵袭,而添加 HIF-1α 则修正了这种作用。体内实验表明,LINC00649 促进了 TNBC 的生长和转移。我们证实 LINC00649 与 NF90/NF45 复合物相互作用,增加 HIF-1α 的 mRNA 稳定性并上调其表达,从而诱导 TNBC 细胞的增殖、侵袭和迁移以及肿瘤的生长和转移。

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