American Association for Cancer Research
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Supplementary Figures S1-S11 from Ablation of miR-10b Suppresses Oncogene-Induced Mammary Tumorigenesis and Metastasis and Reactivates Tumor-Suppressive Pathways

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posted on 2023-03-31, 00:25 authored by Jongchan Kim, Ashley N. Siverly, Dahu Chen, Min Wang, Yuan Yuan, Yumeng Wang, Hyemin Lee, Jinsong Zhang, William J. Muller, Han Liang, Boyi Gan, Xianbin Yang, Yutong Sun, M. James You, Li Ma

Figure S1. Detection of miR-10b, miR-10a, Hoxd4, and Hoxd3. Figure S2. Body and organ weight. Figure S3. Overall survival and fertility. Figure S4. Complete blood cell count. Figure S5. Organ histology. Figure S6. Mammary tumor cell proliferation. Figure S7. PyMT antibody characterization. Figure S8. miR-10b target screen. Figure S9. TBX5 target identification. Figure S10. TBX5 inhibits breast cancer cell proliferation, migration, and invasion. Figure S11. Clinical correlation.

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ARTICLE ABSTRACT

The invasive and metastatic properties of many human tumors have been associated with upregulation of the miRNA miR-10b, but its functional contributions in this setting have not been fully unraveled. Here, we report the generation of miR-10b–deficient mice, in which miR-10b is shown to be largely dispensable for normal development but critical to tumorigenesis. Loss of miR-10b delays oncogene-induced mammary tumorigenesis and suppresses epithelial–mesenchymal transition, intravasation, and metastasis in a mouse model of metastatic breast cancer. Among the target genes of miR-10b, the tumor suppressor genes Tbx5 and Pten and the metastasis suppressor gene Hoxd10 are significantly upregulated by miR-10b deletion. Mechanistically, miR-10b promotes breast cancer cell proliferation, migration, and invasion through inhibition of the expression of the transcription factor TBX5, leading to repression of the tumor suppressor genes DYRK1A and PTEN. In clinical specimens of breast cancer, the expression of TBX5, HOXD10, and DYRK1A correlates with relapse-free survival and overall survival outcomes in patients. Our results establish miR-10b as an oncomiR that drives metastasis, termed a metastamiR, and define the set of critical tumor suppressor mechanisms it overcomes to drive breast cancer progression. Cancer Res; 76(21); 6424–35. ©2016 AACR.

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