P2RY1

Official Full Name

purinergic receptor P2Y1

Organism

Homo sapiens

GeneID

5028

Background

The product of this gene belongs to the family of G-protein coupled receptors. This family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. This receptor functions as a receptor for extracellular ATP and ADP. In platelets binding to ADP leads to mobilization of intracellular calcium ions via activation of phospholipase C, a change in platelet shape, and probably to platelet aggregation. [provided by RefSeq, Jul 2008]

Synonyms

P2Y1; SARCC;

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Detailed Information

Hypermethylated P2RY1 activation can mitigate gastric cancer through apoptosis promotion and proliferation inhibition

With increasing numbers of deaths and high prevalence worldwide, Gastric cancer has been getting growing concerns. However, the etiology of gastric cancer carcinogenesis is multifactorial, and accompanied with various genetic alterations identifications associated with gastric tumorigenesis and progression. Gastric cancers can be classified into two types according to histological differences, epidemiology, etiology, pathogenesis and biological behavior, one is diffuse type, which is characterized by its infiltrating cells and no cohesive cancer cells with vast fibrous stroma, the other one is the intestinal type, which is featured with cohesive and glandular-like cells. Nowadays chemotherapy and molecular targeted therapy are considered as the main approaches for diffuse gastric cancer treatment.

It has been known that activation of ERK signaling led to cancer by P2RY1 receptor, whose DNA methylation states and its corresponding regulatory mechanism remain unrevealed. So, DNA methylation chip was adopted for profiling of genome-wide DNA methylation level in gastric cancer tissues. And proliferation and apoptosis of the SGC7901 gastric cancer cell line were measured after treatment with MRS2365, an apoptosis of P2RY1 receptor. Highly methylation with 4 hypermethylated sites was found in the promoter region of P2RY1 of the diffuse gastric cancer, and it was further validated by bioinformatic analysis in TCGA database. Annexin-V/PI staining and caspase-3 activity assays were chosen for indication of the MRS2365 induced apoptosis in SGC7901 cells. Reduced expression of P2RY1's mRNA induced by high DNA methylation in the promoter region of P2RY1 is echoed with 'aggressivity' of the diffuse type gastric cancer.

P2RY1 receptors work as a novel target for airway disease

A paper in cell reported purinergic P2RY1 receptors in vagal sensory neurons and their involvement in series airway defense reflexes of guarding airways from external stimulus. In addition to this, P2RY1 neurons were demonstrated as one of the rarely distributed laryngeal sensory neurons, and capable of protecting our airways from blockings of ingested food and drinks. Purinergic P2RY1 receptors in vagal sensory neurons function as a sensory neuron for airway threats detection and coordinators for defensive reflexes to guard airway integrity. Experimental methods included genetically modified mouse lines and single-cell RNA sequencing were chosen for the investigation of targeting strategy or sensory molecular diversity of specific sensory neurons. And more advanced techniques, such as optogenetics, chemogenetics, calcium imaging were deployed to understand the diversity of vagal P2RY1 sensory neurons and their central mechanism of guarding respiratory tract from external assaults.

P2RY1 Figure 1. The illustration of MRS2365 affecting RAS-RAF-MEK-ERK signaling pathway by P2RY1 receptor (Hua et al., 2021).

References:

Yinggang Hua, Liangliang Cai, Guoyan Liu, et al. Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation. World Journal of Surgical Oncology, doi: 10.21203/rs.3.rs-351723/v1.
Juan Liu, Yu-Shi Hu, Yong Tang, et al. Commentary: Vagal P2RY1 Receptors: A Novel Target for Airway Disease. Frontiers in Pharmacology, doi:10.1016/j.cell.2020.03.004.
Moayedi, Y., Pitman, M. J., and de Nooij, J. C, et al. Airway protection-A role for vagal P2RY1 receptors. Cell. doi: 10.1016/j.cell.2020.04.006.

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