American Association for Cancer Research
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Supplementary Figure Legends 1-6, Methods from Pivotal Role of Reduced let-7g Expression in Breast Cancer Invasion and Metastasis

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posted on 2023-03-30, 20:52 authored by Pengxu Qian, Zehua Zuo, Zhengsheng Wu, Xianyi Meng, Gaopeng Li, Zhengzhou Wu, Weijie Zhang, Sheng Tan, Vijay Pandey, Yandan Yao, Puyue Wang, Liqing Zhao, Jun Wang, Qiang Wu, Erwei Song, Peter E. Lobie, Zhinan Yin, Tao Zhu

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Screening of the entire let-7 family of microRNAs (miRNA) by in situ hybridization identified let-7g as the only member, the diminished expression of which was significantly associated with lymph node metastasis and poor survival in breast cancer patients. Abrogation of let-7g expression in otherwise nonmetastatic mammary carcinoma cells elicited rapid metastasis from the orthotopic location, through preferential targets, Grb2-associated binding protein 2 (GAB2) and fibronectin 1 (FN1), and consequent activation of p44/42 mitogen-activated protein kinase (MAPK) and specific matrix metalloproteinases. Treatment with estrogen or epidermal growth factor specifically reduced the expression of mature let-7g through activation of p44/42 MAPK and subsequently stimulated expression of GAB2 and FN1, which, in turn, promoted tumor invasion. We thus identify let-7g as a unique member of the let-7 miRNA family that can serve as a prognostic biomarker in breast cancer and also propose a paradigm used by specific signaling molecules via let-7g to cooperatively promote breast cancer invasion and metastasis. Thus, let-7 family members neither possess equivalent clinicopathologic correlation nor function in breast cancer. Cancer Res; 71(20); 6463–74. ©2011 AACR.

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