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

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

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. dw417@sina.com.
  • 5 Department of Breast Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China. Betty-1008@163.com.
  • 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. xiexh@sysucc.org.cn.
  • # 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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