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

Research Paper

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

Peng-Chao Hu1,2,4*, Kai Li2*, Yi-Hao Tian3*, Wen-Ting Pan2, Ying Wang2, Xiao-Long Xu2, Yan-Qi He2, Yang Gao2, Lei Wei2, Jing-Wei Zhang1✉

1. 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.
2. Department of Pathology and Pathophysiology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei, China.
3. Department of Anatomy, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei, China.
4. Department of oncology, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang 441000, Hubei, China.
* These authors contributed equally to this work.

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Citation:
Hu PC, Li K, Tian YH, Pan WT, Wang Y, Xu XL, He YQ, Gao Y, Wei L, Zhang JW. CREB1/Lin28/miR-638/VASP Interactive Network Drives the Development of Breast Cancer. Int J Biol Sci 2019; 15(12):2733-2749. doi:10.7150/ijbs.36854. Available from http://www.ijbs.com/v15p2733.htm

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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.

Keywords: CREB1, Lin28, miR-638, VASP, breast cancer, cell proliferation, metastasis.