Yin Yang 1 suppresses tumor invasion and metastasis in nasopharyngeal carcinoma by negatively regulating eIF4E transcriptional activity and expression

Mengna Li; Yumei Duan; Jianxia Wei; Shipeng Chen; Changning Xue; Lemei Zheng; Hongyu Deng; Songqing Fan; Wei Xiong; Guiyuan Li; Ming Tan; Faqing Tang; Kelin She; Ming Zhou

Yin Yang 1 suppresses tumor invasion and metastasis in nasopharyngeal carcinoma by negatively regulating eIF4E transcriptional activity and expression

Am J Cancer Res. 2023 Aug 15;13(8):3763-3780. eCollection 2023.

Authors

Mengna Li^{1

2

3}, Yumei Duan^{1

2

4}, Jianxia Wei^{1

2

3}, Shipeng Chen^{1

2

3}, Changning Xue^{1

2

3}, Lemei Zheng^{1

2

3}, Hongyu Deng^{1

2}, Songqing Fan⁵, Wei Xiong^{1

2

3}, Guiyuan Li^{1

2

3}, Ming Tan⁶, Faqing Tang¹, Kelin She^{1

2

7}, Ming Zhou^{1

2

3}

Affiliations

¹ NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University Changsha 410078, Hunan, China.
² Cancer Research Institute and School of Basic Medical Sciences, Central South University Changsha 410078, Hunan, China.
³ The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Central South University Changsha 410078, Hunan, China.
⁴ Department of Pathology, Xiangya Hospital, Central South University Changsha 410008, Hunan, China.
⁵ Department of Pathology, The Second Xiangya Hospital, Central South University Changsha 410011, Hunan, China.
⁶ Graduate Institute of Biomedical Sciences and Research Center for Cancer Biology, China Medical University Taichung 406040, Taiwan.
⁷ Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Nomal University Changsha 410005, Hunan, China.

PMID: 37693135
PMCID: PMC10492101

Abstract

Tumor metastasis is a leading cause of death in nasopharyngeal carcinoma (NPC) patients. Previous research has identified that transcription factor Yin Yang 1 (YY1) acts as a tumor suppressor that inhibits cell proliferation and tumor growth in NPC; however, the role and the molecular mechanisms of YY1 in NPC invasion and metastasis remain unclear. In this study, we discovered that YY1 could inhibit the migration and invasion of NPC cells in vitro as well as NPC xenograft tumor metastasis in vivo. Furthermore, we identified eIF4E as a direct downstream target of YY1, and YY1 could negatively regulate the expression of eIF4E at transcriptional level. Moreover, we found that eIF4E promoted the migration and invasion of NPC cells as well as NPC lung metastasis, suggesting its potential as a pro-metastatic mediator in NPC. Importantly, restoring eIF4E expression could partially reverse the inhibitory effects of YY1 on NPC malignancy. In consistent with these findings, the expression of YY1 was downregulated while eIF4E was upregulated in NPC patients with metastasis, and there was a negative correlation between YY1 and eIF4E expression. Collectively, our results indicate that YY1 suppresses the invasion and metastasis of NPC by negatively regulating eIF4E transcription. Therefore, targeting the YY1/eIF4E transcriptional axis could be a potential therapeutic strategy for the treatment of patients with NPC.

Keywords: Nasopharyngeal carcinoma; YY1; eIF4E; transcription activity; tumor metastasis.