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CREB1/Lin28/miR-638/VASP 相互作用网络驱动乳腺癌的发展。

CREB1/Lin28/miR-638/VASP Interactive Network Drives the Development of Breast Cancer.

机构信息

Department of Breast and Thyroid Surgery, Zhongnan Hospital, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan University, Wuhan 430071, Hubei, China.

Department of Pathology and Pathophysiology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei, China.

出版信息

Int J Biol Sci. 2019 Oct 21;15(12):2733-2749. doi: 10.7150/ijbs.36854. eCollection 2019.

Abstract

Breast cancer is one of the most common malignant tumors worldwide. Metastasis remains the leading cause of death in breast cancer patients. Research on the mechanism of breast cancer metastasis has become a core issue in breast cancer research. Our previous series of studies have shown that VASP, as a key oncogene, plays an important role in the development of various tumors such as breast cancer. In this study, we find that miR-638 can target to inhibit VASP expression, and Lin28 acts as an RNA-binding protein to regulate the processing of miR-638, which inhibits its maturation and promotes the expression of VASP. In addition, we also find that CREB1 acts as a transcription factor that binds to the promoter of Lin28 gene and activates the Lin28/miR-638/VASP pathway. Furthermore, CREB1 can also directly bind to the promoter of VASP, and activate VASP expression, forming a CREB/Lin28/miR-638/VASP interactive network, which plays an important role in promoting cell proliferation and migration in breast cancer. Our study explained the mechanism of CREB1/Lin28/miR-638/VASP network promoting the development of breast cancer, which further elucidated the mechanism of VASP as a key oncogene, and also provided a theoretical basis for expanding new approaches to tumor biotherapy.

摘要

乳腺癌是全球最常见的恶性肿瘤之一。转移仍然是乳腺癌患者死亡的主要原因。对乳腺癌转移机制的研究已成为乳腺癌研究的核心问题。我们之前的一系列研究表明,VASP 作为一个关键的癌基因,在乳腺癌等各种肿瘤的发展中起着重要作用。在这项研究中,我们发现 miR-638 可以靶向抑制 VASP 的表达,Lin28 作为一种 RNA 结合蛋白,调节 miR-638 的加工,抑制其成熟并促进 VASP 的表达。此外,我们还发现 CREB1 作为转录因子,与 Lin28 基因的启动子结合,激活 Lin28/miR-638/VASP 通路。此外,CREB1 还可以直接与 VASP 的启动子结合,激活 VASP 的表达,形成 CREB/Lin28/miR-638/VASP 互作网络,在促进乳腺癌细胞增殖和迁移中发挥重要作用。我们的研究解释了 CREB1/Lin28/miR-638/VASP 网络促进乳腺癌发展的机制,进一步阐明了 VASP 作为关键癌基因的作用机制,也为拓展肿瘤生物治疗的新方法提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f99e/6854368/b01987ac2c8f/ijbsv15p2733g001.jpg

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