PIWI-interacting RNA-YBX1 inhibits proliferation and metastasis by the MAPK signaling pathway via YBX1 in triple-negative breast cancer

  • Cell Death Discov. 2024 Jan 5;10(1):7. doi: 10.1038/s41420-023-01771-w.
Linyu Wu  #  1 ,  Shanshan Huang  #  1 ,  Wenwen Tian  #  2 ,  Peng Liu  1 ,  Yi Xie  1 ,  Yu Qiu  1 ,  Xing Li  1 ,  Yuhui Tang  1 ,  Shaoquan Zheng  3 ,  Yuying Sun  1 ,  Hailin Tang  1 ,  Wei Du  4 ,  Weige Tan  5 ,  Xinhua Xie  6
Affiliations
  • 1. State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
  • 2. Affiliated Cancer Hospital & Institute of Guangzhou Medical University, No.78 Hengzhigang Road, Guangzhou, 510095, China.
  • 3. Department of Breast Surgery, Breast Disease Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
  • 4. Department of Pathology, Changde Hospital, Xiangya School of Medicine, Central South University, Changde, 415003, China. [email protected].
  • 5. Department of Breast Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China. [email protected].
  • 6. State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. [email protected].
  • # Contributed equally.
PMID: 38182573 DOI: 10.1038/s41420-023-01771-w
Abstract

Breast Cancer is the second leading cause of death in women worldwide, with Triple-Negative Breast Cancer (TNBC) having the worst prognosis. Although there are numerous studies on TNBC, there is no effective treatment for it, and it is still a major problem today. Studies on PIWI-interacting RNAs (piRNAs) are increasing and investigating the mechanism of piRNAs in the proliferation and metastasis of TNBC may lead to new potential treatment targets. Here, we identified a novel piRNA, piR-YBX1, which was downregulated in TNBC compared to matched normal breast tissue. Overexpression of piR-YBX1 significantly inhibited the proliferation, migration, invasion ability of TNBC cells both in vivo and in vitro. Mechanistically, piR-YBX1 could bind directly to mRNA of Y-box binding protein 1 (YBX1) and overexpression of piR-YBX1 downregulated YBX1 in both mRNA and protein levels, while the function of piR-YBX1 could be partly rescued by overexpression of YBX1. In addition, YBX1 could bind to RAF1 which is the key molecule in the MAPK signaling pathway, and overexpression of piR-YBX1 inhibited the p-MEK and p-ERK1/2, which can be reverted by YBX1. In conclusion, our findings discovered that the piR-YBX1/YBX1/MAPK axis suppresses the proliferation and metastasis of TNBC and therefore piR-YBX1 has the potential to be an effective therapeutic agent for Breast Cancer.

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