Effect of the transcription factor YY1 on the development of pancreatic endocrine and exocrine tumors: a narrative review

Qun Chen,Hao Yuan,Ling-Dong Meng,Wu-Jun Wang,Peng Shen,Tao-Yue Yang,Wan-Li Ge,Xu-Min Huang,Jing-Jing Zhang,Yun-Xuan Jia,Yi Miao,Kui-Rong Jiang,Peng-Fei Wu

doi:10.1186/s13578-021-00602-8

Qun Chen, Hao Yuan + Show 11 more

Open Access

https://doi.org/10.1186/s13578-021-00602-8

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Abstract

Pancreatic tumors are classified into endocrine and exocrine types, and the clinical manifestations in patients are nonspecific. Most patients, especially those with pancreatic ductal adenocarcinoma (PDAC), have lost the opportunity to receive for the best treatment at the time of diagnosis. Although chemotherapy and radiotherapy have shown good therapeutic results in other tumors, their therapeutic effects on pancreatic tumors are minimal. A multifunctional transcription factor, Yin-Yang 1 (YY1) regulates the transcription of a variety of important genes and plays a significant role in diverse tumors. Studies have shown that targeting YY1 can improve the survival time of patients with tumors. In this review, we focused on the mechanism by which YY1 affects the occurrence and development of pancreatic tumors. We found that a YY1 mutation is specific for insulinomas and has a role in driving the degree of malignancy. In addition, changes in the circadian network are a key causative factor of PDAC. YY1 promotes pancreatic clock progression and induces malignant changes, but YY1 seems to act as a tumor suppressor in PDAC and affects many biological behaviors, such as proliferation, migration, apoptosis and metastasis. Our review summarizes the progress in understanding the role of YY1 in pancreatic endocrine and exocrine tumors and provides a reasonable assessment of the potential for therapeutic targeting of YY1 in pancreatic tumors.

Highlights

As the second largest digestive gland of the human body, the pancreas is located behind the peritoneum and has both exocrine and endocrine functions [1, 2]
Irshad, et al did not find the Yin-Yang 1 (YY1) p.T372R heterozygous mutation in the Indian population, Cao, Cromer, and Wang, et al confirmed that the mutation is present in the Chinese and the American populations and in the German population
The YY1 p.T372R mutation is a specific mutation that is different from mutations observed in pancreatic tumors that do not secrete insulin and in pancreatic ductal adenocarcinoma (PDAC)

Summary

Background

As the second largest digestive gland of the human body, the pancreas is located behind the peritoneum and has both exocrine and endocrine functions [1, 2]. YY1 inhibits MUC4 gene transcription and expression by binding to a suppressor element in the MUC4 promoter, resulting in decreased phosphorylation of downstream ErbB2 and phosphorylation of p38/MAPK [75] This pattern indicates activation of the ErbB2 and p38/ MAPK pathways after YY1 silencing, thereby resulting in suppressed invasion and metastasis of PDAC cells [55]. Another study showed that KRAS mutation can activate the transcription factor YY1 through inflammatory NF-κB signaling, subsequently inhibiting the expression of the tumor suppressor gene miR-489, which affects the ability of PDAC cells to migrate and metastasize [71]. This feedback loop might be a protective mechanism supplied by the human body

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Conclusion