Abstract 2374: Mir-29/Hsp47 regulate breast cancer progression by modulating the ECM transcription network

Abstract

Abstract The extracellular matrix (ECM), an essential component of tumor microenvironment, play crucial roles in cancer development and progression. Using gene co-expression network analysis, we have identified an ECM transcription network from hundreds of human breast cancer. In this report, we show how the molecular chaperone protein Hsp47 functions as a nodal hub in regulating an ECM gene transcription network. We found that Hsp47 expression was activated during breast cancer development and progression. Hsp47 silencing reprogrammed human breast cancer cells to form growth-arrested and/or non-invasive structures in 3D cultures, and to limit tumor growth in xenograft assays by reducing deposition of collagen and fibronectin. Co-expression network analysis also showed that levels of microRNA-29b and 29c were inversely correlated with expression of Hsp47 and ECM network genes in human breast cancer tissues. We found that miR-29 repressed expression of Hsp47 along with multiple ECM network genes. Ectopic expression of miR-29b suppressed malignant phenotypes of breast cancer cells in 3D culture. Clinically, increased expression of Hsp47 and reduced levels of miR-29b and 29c were associated with poor survival outcomes in breast cancer patients. Our results show that Hsp47 is regulated by miR-29 during breast cancer development and progression, and that increased Hsp47 expression promotes cancer progression in part by enhancing deposition of ECM proteins. Citation Format: Jieqing Zhu, Gaofeng Xiong, Ren Xu. Mir-29/Hsp47 regulate breast cancer progression by modulating the ECM transcription network. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2374. doi:10.1158/1538-7445.AM2015-2374