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Theranostics 2023; 13(7):2337-2349. doi:10.7150/thno.82538 This issue Cite

Research Paper

IL11 signaling mediates piR-2158 suppression of cell stemness and angiogenesis in breast cancer

Qian Zhao1†, Lu Qian1†, Yuefan Guo1†, Jinhui Lü1, Danni Li1, Heying Xie1,2, Qiong Wang1, Wenjing Ma1, Pengfei Liu1, Yu Liu1,2, Tao Wang1, Xuebiao Wu3, Junyi Han1✉, Zuoren Yu1✉

1. Key Laboratory of Arrhythmias of the Ministry of Education of China, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
2. School of Basic Medicine, Jinzhou Medical University, Liaoning, China.
3. Shanghai OE Biotech Co., Ltd., Shanghai, China.
†Equal contribution to the work.

✉ Corresponding authors: Zuoren Yu, Ph.D., Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China; Email: zuoren.yuedu.cn. Or Junyi Han, M.D; Email: docto More

Citation:
Zhao Q, Qian L, Guo Y, Lü J, Li D, Xie H, Wang Q, Ma W, Liu P, Liu Y, Wang T, Wu X, Han J, Yu Z. IL11 signaling mediates piR-2158 suppression of cell stemness and angiogenesis in breast cancer. Theranostics 2023; 13(7):2337-2349. doi:10.7150/thno.82538. https://www.thno.org/v13p2337.htm
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Abstract

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Emerging evidence has indicated the aberrant expression of PIWI-interacting RNAs (piRNAs) in human cancer cells to regulate tumor development and progression by governing cancer cell stemness. Herein, we identified downregulation of piR-2158 in human breast cancer tumors, especially in ALDH+ breast cancer stem cells (BCSCs) from patients and cell lines, which was further validated in two types of genetically engineered mouse models of breast cancer (MMTV-Wnt and MMTV-PyMT). Enforced overexpression of piR-2158 in basal-like or luminal subtypes of breast cancer cells suppressed cell proliferation, migration, epithelial-mesenchymal transition (EMT) and stemness in vitro. Administration of a dual mammary tumor-targeting piRNA delivery system in mice reduced tumor growth in vivo. RNA-seq, ChIP-seq and luciferase reporter assays demonstrated piR-2158 as a transcriptional repressor of IL11 by competing with AP-1 transcription factor subunit FOSL1 to bind the promoter of IL11. STAT3 signaling mediated piR-2158-IL11 regulation of cancer cell stemness and tumor growth. Moreover, by co-culturing of MDA-MB-231 and HUVECs in vitro and CD31 staining of tumor endothelial cells in vivo, we demonstrated inhibition of angiogenesis by piR-2158-IL11 in breast cancer. In conclusion, the current study not only reveals a novel mechanism through which piR-2158 inhibits mammary gland tumorigenesis via regulating cancer stem cells and tumor angiogenesis, but also provides a novel therapeutic strategy in treatment of breast cancer.

Keywords: piR-2158, breast cancer, cancer stem cell, IL-11

Citation styles

APA
Zhao, Q., Qian, L., Guo, Y., Lü, J., Li, D., Xie, H., Wang, Q., Ma, W., Liu, P., Liu, Y., Wang, T., Wu, X., Han, J., Yu, Z. (2023). IL11 signaling mediates piR-2158 suppression of cell stemness and angiogenesis in breast cancer. Theranostics, 13(7), 2337-2349. https://doi.org/10.7150/thno.82538.

ACS
Zhao, Q.; Qian, L.; Guo, Y.; Lü, J.; Li, D.; Xie, H.; Wang, Q.; Ma, W.; Liu, P.; Liu, Y.; Wang, T.; Wu, X.; Han, J.; Yu, Z. IL11 signaling mediates piR-2158 suppression of cell stemness and angiogenesis in breast cancer. Theranostics 2023, 13 (7), 2337-2349. DOI: 10.7150/thno.82538.

NLM
Zhao Q, Qian L, Guo Y, Lü J, Li D, Xie H, Wang Q, Ma W, Liu P, Liu Y, Wang T, Wu X, Han J, Yu Z. IL11 signaling mediates piR-2158 suppression of cell stemness and angiogenesis in breast cancer. Theranostics 2023; 13(7):2337-2349. doi:10.7150/thno.82538. https://www.thno.org/v13p2337.htm

CSE
Zhao Q, Qian L, Guo Y, Lü J, Li D, Xie H, Wang Q, Ma W, Liu P, Liu Y, Wang T, Wu X, Han J, Yu Z. 2023. IL11 signaling mediates piR-2158 suppression of cell stemness and angiogenesis in breast cancer. Theranostics. 13(7):2337-2349.

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