Zinc-finger protein YY1 suppresses tumor growth of human nasopharyngeal carcinoma by inactivating c-Myc-mediated microRNA-141 transcription.

Abstract

Yin Yang 1 (YY1) is a zinc-finger protein that plays critical roles in various biological processes by interacting with DNA and numerous protein partners. YY1 has been reported to play dual biological functions as either an oncogene or tumor suppressor in the development and progression of multiple cancers, but its role in human nasopharyngeal carcinoma (NPC) has not yet been revealed. In this study, we found that YY1 overexpression significantly inhibits cell proliferation and cell-cycle progression from G1 to S and promotes apoptosis in NPC cells. Moreover, we identified YY1 as a component of the c-Myc complex and observed that ectopic expression of YY1 inhibits c-Myc transcriptional activity, as well as the promoter activity and expression of the c-Myc target gene microRNA-141 (miR-141). Furthermore, restoring miR-141 expression could at least partially reverse the inhibitory effect of YY1 on cell proliferation and tumor growth and on the expression of some critical c-Myc targets, such as PTEN/AKT pathway components both in vitro and in vivo We also found that YY1 expression is reduced in NPC tissues, negatively correlates with miR-141 expression and clinical stages in NPC patients, and positively correlates with survival prognosis. Our results reveal a previously unappreciated mechanism in which the YY1/c-Myc/miR-141 axis plays a critical role in NPC progression and may provide some potential and valuable targets for the diagnosis and treatment of NPC.

• Authors: Mengna Li, Yukun Liu, Yanmei Wei, Chunchun Wu, Hanbing Meng, Weihong Niu, Yao Zhou, Heran Wang, Qiuyuan Wen, Songqing Fan, Zheng Li, Xiayu Li, Jianda Zhou, Ke Cao, Wei Xiong, Zhaoyang Zeng, Xiaoling Li, Yuanzheng Qiu, Guiyuan Li, Ming Zhou
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 294 Issue 15 Pg. 6172-6187 (04 12 2019) ISSN: 1083-351X [Electronic] United States
• PMID: 30718276 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Li et al.

Chemical References

• MIRN141 microRNA, human
• MYC protein, human
• MicroRNAs
• Proto-Oncogene Proteins c-myc
• RNA, Neoplasm
• Tumor Suppressor Proteins
• YY1 Transcription Factor
• YY1 protein, human

Topics

• Adult
• Cell Line, Tumor
• Female
• Humans
• Male
• MicroRNAs (biosynthesis, genetics)
• Middle Aged
• Nasopharyngeal Carcinoma (genetics, metabolism, pathology)
• Nasopharyngeal Neoplasms (genetics, metabolism, pathology)
• Proto-Oncogene Proteins c-myc (genetics, metabolism)
• RNA, Neoplasm (biosynthesis, genetics)
• Transcription, Genetic
• Tumor Suppressor Proteins (genetics, metabolism)
• YY1 Transcription Factor (genetics, metabolism)