Pleiotropic physiological functions of Piezo1 in human body and its effect on malignant behavior of tumors.

Mechanosensitive ion channel protein 1 (Piezo1) is a large homotrimeric membrane protein. Piezo1 has various effects and plays an important and irreplaceable role in the maintenance of human life activities and homeostasis of the internal environment. In addition, recent studies have shown that Piezo1 plays a vital role in tumorigenesis, progression, malignancy and clinical prognosis. Piezo1 is involved in regulating the malignant behaviors of a variety of tumors, including cellular metabolic reprogramming, unlimited proliferation, inhibition of apoptosis, maintenance of stemness, angiogenesis, invasion and metastasis. Moreover, Piezo1 regulates tumor progression by affecting the recruitment, activation, and differentiation of multiple immune cells. Therefore, Piezo1 has excellent potential as an anti-tumor target. The article reviews the diverse physiological functions of Piezo1 in the human body and its major cellular pathways during disease development, and describes in detail the specific mechanisms by which Piezo1 affects the malignant behavior of tumors and its recent progress as a new target for tumor therapy, providing new perspectives for exploring more potential effects on physiological functions and its application in tumor therapy.

LINK-A: unveiling its functional role and clinical significance in human tumors.

LINK-A, also recognized as LINC01139, has emerged as a key oncological lncRNA in cancer. LINK-A is upregulated in solid and liquid tumor samples, including breast cancer, ovarian cancer, glioma, non-small-cell lung cancer, and mantle cell lymphoma. Notably, LINK-A is involved in regulating critical cancer-related pathways, such as AKT and HIF1α signaling, and is implicated in a range of oncogenic activities, including cell proliferation, apoptosis, epithelial-mesenchymal transition (EMT), cell invasion and migration, and glycolysis reprogramming. LINK-A's differential expression and its correlation with clinical features enable it to be a promising biomarker for cancer diagnosis, prognosis, and the stratification of tumor progression. Additionally, LINK-A's contribution to the development of resistance to cancer therapies, including AKT inhibitors and immunotherapy, underscores its potential as a therapeutic target. This review provides a comprehensive overview of the available data on LINK-A, focusing on its molecular regulatory pathways and clinical significance. By exploring the multifaceted nature of LINK-A in cancer, the review aims to offer a valuable resource for future research directions, potentially guiding the development of novel therapeutic strategies targeting this lncRNA in cancer treatment.

Biological roles of SLC16A1-AS1 lncRNA and its clinical impacts in tumors.

Recent studies have increasingly highlighted the aberrant expression of SLC16A1-AS1 in a variety of tumor types, where it functions as either an oncogene or a tumor suppressor in the pathogenesis of different cancers. The expression levels of SLC16A1-AS1 have been found to significantly correlate with clinical features and the prognosis of cancer patients. Furthermore, SLC16A1-AS1 modulates a range of cellular functions, including proliferation, migration, and invasion, through its interactions with diverse molecules and signaling pathways. This review examines the latest evidence regarding the role of SLC16A1-AS1 in the progression of various tumors and explores its potential clinical applications as a novel prognostic and diagnostic biomarker. Our comprehensive review aims to deepen the understanding of SLC16A1-AS1's multifaceted role in oncology, underscoring its potential as a significant biomarker and therapeutic target.

Olfactory ensheathing cells as candidate cells for chronic pain treatment.

Chronic pain is often accompanied by tissue damage and pain hypersensitivity. It easily relapses and is challenging to cure, which seriously affects the patients' quality of life and is an urgent problem to be solved. Current treatment methods primarily rely on morphine drugs, which do not address the underlying nerve injury and may cause adverse reactions. Therefore, in recent years, scientists have shifted their focus from chronic pain treatment to cell transplantation. This review describes the classification and mechanism of chronic pain through the introduction of the characteristics of olfactory ensheathing cells (OECs), an in-depth discussion of special glial cells through the phagocytosis of nerve debris, receptor-ligand interactions, providing nutrition, and other inhibition of neuroinflammation, and ultimately supporting axon regeneration and mitigation of chronic pain. This review summarizes the potential and limitations of OECs for treating chronic pain by objectively analyzing relevant clinical trials and methods to enhance efficacy and future development prospects.

LINC00839 in Human Disorders: Insights into its Regulatory Roles and Clinical Impact, with a Special Focus on Cancer.

LINC00839 has captured significant attention within a spectrum of human disorders, including acute lung injury, osteoarthritis, and childhood obesity. Notably, aberrant expression patterns of LINC00839 have been observed across diverse cancer tissues and cell lines. LINC00839 emerges as an oncogenic factor in tumorigenesis and exerts a positive influence on tumor-associated behaviors. Its therapeutic potential for various cancers is underscored by its modulatory impact on pivotal signaling pathways, such as PI3K/AKT, OXPHOS, and Wnt/ß-catenin. Additionally, LINC00839's role in reducing sensitivity to drug and radiotherapy interventions presents opportunities for targeted intervention. Furthermore, elevated LINC00839 expression indicates advanced clinicopathological features and foretells unfavorable prognoses, as validated by publications and comprehensive analyses of tumor types using TCGA datasets. This review elucidates the multiple regulatory mechanisms and functional implications of LINC00839 in various diseases, especially malignancies, emphasizing its potential as a predictive biomarker and therapeutic target across multiple disease domains in humans.

LINC01134: a pivotal oncogene with promising predictive maker and therapeutic target in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) represents a leading and fatal malignancy within the gastrointestinal tract. Recent advancements highlight the pivotal role of long non-coding RNAs (lncRNAs) in diverse biological pathways and pathologies, particularly in tumorigenesis. LINC01134, a particular lncRNA, has attracted considerable attention due to its oncogenic potential in hepatoma. Current research underscores LINC01134's potential in augmenting the onset and progression of HCC, with notable implications in drug resistance. This review comprehensively explores the molecular functions and regulatory mechanisms of LINC01134 in HCC, offering a fresh perspective for therapeutic interventions. By delving into LINC01134's multifaceted roles, we aim to foster novel strategies in HCC management.

Role and therapeutic targets of P2X7 receptors in neurodegenerative diseases.

The P2X7 receptor (P2X7R), a non-selective cation channel modulated by adenosine triphosphate (ATP), localizes to microglia, astrocytes, oligodendrocytes, and neurons in the central nervous system, with the most incredible abundance in microglia. P2X7R partake in various signaling pathways, engaging in the immune response, the release of neurotransmitters, oxidative stress, cell division, and programmed cell death. When neurodegenerative diseases result in neuronal apoptosis and necrosis, ATP activates the P2X7R. This activation induces the release of biologically active molecules such as pro-inflammatory cytokines, chemokines, proteases, reactive oxygen species, and excitotoxic glutamate/ATP. Subsequently, this leads to neuroinflammation, which exacerbates neuronal involvement. The P2X7R is essential in the development of neurodegenerative diseases. This implies that it has potential as a drug target and could be treated using P2X7R antagonists that are able to cross the blood-brain barrier. This review will comprehensively and objectively discuss recent research breakthroughs on P2X7R genes, their structural features, functional properties, signaling pathways, and their roles in neurodegenerative diseases and possible therapies.

DARS-AS1: A Vital Oncogenic LncRNA Regulator with Potential for Cancer Prognosis and Therapy.

DARS-AS1, short for Aspartyl-tRNA synthetase antisense RNA 1, has emerged as a pivotal player in cancers. Upregulation of this lncRNA is a recurrent phenomenon observed across various cancer types, where it predominantly assumes oncogenic roles, exerting influence on multiple facets of tumor cell biology. This aberrant expression of DARS-AS1 has triggered extensive research investigations, aiming to unravel its roles and clinical values in cancer. In this review, we elucidate the significant correlation between dysregulated DARS-AS1 expression and adverse survival prognoses in cancer patients, drawing from existing literature and pan-cancer analyses from The Cancer Genome Atlas (TCGA). Additionally, we provide comprehensive insights into the diverse functions of DARS-AS1 in various cancers. Our review encompasses the elucidation of the molecular mechanisms, ceRNA networks, functional mediators, and signaling pathways, as well as its involvement in therapy resistance, coupled with the latest advancements in DARS-AS1-related cancer research. These recent updates enrich our comprehensive comprehension of the pivotal role played by DARS-AS1 in cancer, thereby paving the way for future applications of DARS-AS1-targeted strategies in tumor prognosis evaluation and therapeutic interventions. This review furnishes valuable insights to advance the ongoing efforts in combating cancer effectively.

LncRNA-MUF: A Novel Oncogenic Star with Potential as a Biological Marker and Therapeutic Target for Gastrointestinal Malignancies.

Gastrointestinal (GI) cancers pose a significant global health challenge, characterized by a high incidence and poor prognosis. The delayed detection and occurrence of metastasis contribute to the overall low survival rates associated with these cancers. Therefore, there is an urgent need to identify novel molecular targets for effective GI cancer treatment. Recent research has shed light on the potential of long non-coding RNAs (lncRNAs) as promising targets in cancer therapy, given their strong association with carcinogenesis and profound impact on tumor development. Among these lncRNAs, lncRNA-MUF, also known as LINC00941, has emerged as a key player in oncogenic regulation, specifically implicated in the progression of various GI cancers, including esophageal, gastric, colorectal, hepatic, and pancreatic cancer. This review aims to provide an updated and focused analysis of the regulatory roles of LINC00941 in the initiation and progression of GI cancer. Our objective is to unravel the underlying molecular mechanisms through which LINC00941 influences GI cancer phenotypes both in vivo and in vitro, with a special emphasis on the key molecules and signaling pathways involved. Additionally, LINC00941 has demonstrated clinical significance in terms of clinical pathology, prognosis, and diagnosis in GI tumors, further reinforcing its potential as a novel therapeutic target.

The feedback loop of EFTUD2/c-MYC impedes chemotherapeutic efficacy by enhancing EFTUD2 transcription and stabilizing c-MYC protein in colorectal cancer.

BACKGROUND: Chemoresistance presents a significant obstacle in the treatment of colorectal cancer (CRC), yet the molecular basis underlying CRC chemoresistance remains poorly understood, impeding the development of new therapeutic interventions. Elongation factor Tu GTP binding domain containing 2 (EFTUD2) has emerged as a potential oncogenic factor implicated in various cancer types, where it fosters tumor growth and survival. However, its specific role in modulating the sensitivity of CRC cells to chemotherapy is still unclear. METHODS: Public dataset analysis and in-house sample validation were conducted to assess the expression of EFTUD2 in 5-fluorouracil (5-FU) chemotherapy-resistant CRC cells and the potential of EFTUD2 as a prognostic indicator for CRC. Experiments both in vitro, including MTT assay, EdU cell proliferation assay, TUNEL assay, and clone formation assay and in vivo, using cell-derived xenograft models, were performed to elucidate the function of EFTUD2 in sensitivity of CRC cells to 5-FU treatment. The molecular mechanism on the reciprocal regulation between EFTUD2 and the oncogenic transcription factor c-MYC was investigated through molecular docking, ubiquitination assay, chromatin immunoprecipitation (ChIP), dual luciferase reporter assay, and co-immunoprecipitation (Co-IP). RESULTS: We found that EFTUD2 expression was positively correlated with 5-FU resistance, higher pathological grade, and poor prognosis in CRC patients. We also demonstrated both in vitro and in vivo that knockdown of EFTUD2 sensitized CRC cells to 5-FU treatment, whereas overexpression of EFTUD2 impaired such sensitivity. Mechanistically, we uncovered that EFTUD2 physically interacted with and stabilized c-MYC protein by preventing its ubiquitin-mediated proteasomal degradation. Intriguingly, we found that c-MYC directly bound to the promoter region of EFTUD2 gene, activating its transcription. Leveraging rescue experiments, we further confirmed that the effect of EFTUD2 on 5-FU resistance was dependent on c-MYC stabilization. CONCLUSION: Our findings revealed a positive feedback loop involving an EFTUD2/c-MYC axis that hampers the efficacy of 5-FU chemotherapy in CRC cells by increasing EFTUD2 transcription and stabilizing c-MYC oncoprotein. This study highlights the potential of EFTUD2 as a promising therapeutic target to surmount chemotherapy resistance in CRC patients.

A concise review of the regulatory, diagnostic, and prognostic implications of HOXB-AS3 in tumors.

Recent studies have reported that HOXB-AS3 (HOXB Cluster Antisense RNA 3) is an intriguing molecule with dual functionality as a long noncoding RNA (lncRNA) and putative coding peptide in tumorigenesis and progression. The significant expression alterations of HOXB-AS3 were detected in diverse cancer types and closely correlated with clinical stage and patient survival. Furthermore, HOXB-AS3 was involved in a spectrum of biological processes in solid tumors and hematological malignancies, such as stemness, lipid metabolism, migration, invasion, and tumor growth. This review comprehensively analyzes its clinical relevance for diagnosis and prognosis across human tumors and summarizes its functional role and regulatory mechanisms in different malignant tumors, including liver cancer, acute myeloid leukemia, ovarian cancer, lung cancer, endometrial carcinoma, colon cancer, and oral squamous cell carcinoma. Overall, HOXB-AS3 emerges as a promising biomarker and novel therapeutic target in multiple human tumors.

A review on the role of gamma-butyrobetaine hydroxylase 1 antisense RNA 1 in the carcinogenesis and tumor progression.

Gamma-butyrobetaine hydroxylase 1 antisense RNA 1 (BBOX1-AS1), located on human chromosome 11 p14, emerges as a critical player in tumorigenesis with diverse oncogenic effects. Aberrant expression of BBOX1-AS1 intricately regulates various cellular processes, including cell growth, epithelial-mesenchymal transition, migration, invasion, metastasis, cell death, and stemness. Notably, the expression of BBOX1-AS1 was significantly correlated with clinical-pathological characteristics and tumor prognoses, and it could also be used for the diagnosis of lung and esophageal cancers. Through its involvement in the ceRNA network, BBOX1-AS1 competitively binds to eight miRNAs in ten different cancer types. Additionally, BBOX1-AS1 can directly modulate downstream protein-coding genes or act as an mRNA stabilizer. The implications of BBOX1-AS1 extend to critical signaling pathways, including Hedgehog, Wnt/ß-catenin, and MELK/FAK pathways. Moreover, it influences drug resistance in hepatocellular carcinoma. The present study provides a systematic review of the clinical significance of BBOX1-AS1's aberrant expression in diverse tumor types. It sheds light on the intricate molecular mechanisms through which BBOX1-AS1 influences cancer initiation and progression and outlines potential avenues for future research in this field.

SRY-box transcription factor 21 antisense divergent transcript 1: Regulatory roles and clinical significance in neoplastic conditions and Alzheimer's Disease.

SRY-box transcription factor 21 antisense divergent transcript 1 (SOX21-AS1) is a multifaceted long non-coding RNA (lncRNA) that plays diverse roles in both neoplastic conditions and Alzheimer's disease. Its aberrant expression intricately regulates a wide spectrum of cellular processes, spanning from epithelial-mesenchymal transition (EMT), apoptosis, migration, metastasis, and stemness to drug resistance. SOX21-AS1 achieves these effects through its involvement in the competitive endogenous RNA (ceRNA) network, modulation of downstream genes, and regulation of critical pathways, including PI3K/AKT, Hippo, Wnt/ß-catenin, and ERK signaling. Of significant clinical relevance, SOX21-AS1 expression has shown robust correlations with various clinical-pathological features. Moreover, it has demonstrated promising prognostic and diagnostic potential across a spectrum of tumors, as evidenced by existing literature and TCGA pan-cancer analyses. In Alzheimer's disease, SOX21-AS1 assumes a distinctive role. It influences neuronal viability, apoptosis, and oxidative stress by interacting with miR-107 and miR-132, and affecting the PI3K/AKT and Wnt signaling pathways. This comprehensive review sheds light on the functions of SOX21-AS1 and the regulated mechanisms underpinning its impact on neoplastic conditions and Alzheimer's disease. It underscores the clinical significance of SOX21-AS1 and positions it as a promising therapeutic target in both the oncological and neurodegenerative domains.

Tumor Suppressor LncRNA on Chromosome 8p12 (TSLNC8): A Concise Review in Human Malignancies.

Tumor Suppressor Long Non-Coding RNA on Chromosome 8p12 (TSLNC8) is an RNA gene that generates a long non-coding RNA transcribed intergenically from both strands. Its significant role in human malignancies attracted significant attention in recent years. Expression analysis of TSLNC8 has been conducted in tissue specimens and cell lines using various techniques, including reverse transcription-quantitative polymerase chain reaction (RT-qPCR), in situ hybridization (ISH), and microarray analysis. Furthermore, functional studies involving the loss and/or gain of TSLNC8 function in cellular and animal models have been carried out. These investigations have highlighted the impact of TSLNC8 on key tumor-related processes, including migration, invasion, and metastasis. Moreover, TSLNC8 has emerged as a regulator capable of modulating critical signaling pathways, such as the Hippo, STAT3, WNT/ß-catenin, and MAPK pathways. In this review, we comprehensively synthesize the findings derived from in vitro and in vivo studies, along with analyses conducted on clinical samples, to provide a comprehensive understanding of the multifaceted role of TSLNC8 as a promising tumor biomarker and a potential target for therapeutic interventions.

HOXC Cluster Antisense RNA 3, a Novel Long Non-Coding RNA as an Oncological Biomarker and Therapeutic Target in Human Malignancies.

HOXC cluster antisense RNA 3 (HOXC-AS3) is a novel long noncoding RNA (lncRNA) that exhibits aberrant expression patterns in various cancer types. Its expression is closely related to clinicopathological features, demonstrating significant clinical relevance across multiple tumors. And HOXC-AS3 plays multifaceted roles in tumor progression, impacting cell proliferation, apoptosis, migration, invasion, epithelial-mesenchymal transition (EMT), autophagy, senescence, tumor growth, and metastasis. In this review, we summarized and comprehensively analyzed the expression and clinical significance of HOXC-AS3 as a diagnostic and prognostic biomarker for malignancies. Additionally, we presented an in-depth update on HOXC-AS3's functions and regulatory mechanisms in cancer pathogenesis. This narrative review underscores the importance of HOXC-AS3 as a promising lncRNA candidate in cancer research and its potential as a predictive biomarker and therapeutic target in clinical applications.

Potential role of Schwann cells in neuropathic pain.

Neuropathic pain (NPP) is a common syndrome associated with most forms of disease, which poses a serious threat to human health. NPP may persist even after the nociceptive stimulation is eliminated, and treatment is extremely challenging in such cases. Schwann cells (SCs) form the myelin sheaths around neuronal axons and play a crucial role in neural information transmission. SCs can secrete trophic factors to nourish and protect axons, and can further secrete pain-related factors to induce pain. SCs may be activated by peripheral nerve injury, triggering the transformation of myelinated and non-myelinated SCs into cell phenotypes that specifically promote repair. These differentiated SCs provide necessary signals and spatial clues for survival, axonal regeneration, and nerve regeneration of damaged neurons. They can further change the microenvironment around the regions of nerve injury, and relieve the pain by repairing the injured nerve. Herein, we provide a comprehensive overview of the biological characteristics of SCs, discuss the relationship between SCs and nerve injury, and explore the potential mechanism of SCs and the occurrence of NPP. Moreover, we summarize the feasible strategies of SCs in the treatment of NPP, and attempt to elucidate the deficiencies and defects of SCs in the treatment of NPP.

Chitosan biomaterial enhances the effect of OECs on the inhibition of sciatic nerve injury-induced neuropathic pain.

Neuropathic pain is a common symptom experienced by most clinical diseases at different levels, and its treatment has always been a clinical difficulty. Therefore, it is particularly important to explore new and effective treatment methods. The role of olfactory ensheathing cells (OECs) in nerve injury and pain is recognized by different studies. Our previous study found that transplantation of OECs alleviated hyperalgesia in rats. However, single-cell transplantation lacks medium adhesion and support, and exerts limited analgesic effect. Therefore, on the basis of the previous study, this study investigated the effect of pain relief by co-transplanting OECs with chitosan (CS) (a biological tissue engineering material, as OECs were transplanted into the host medium) to the injured sciatic nerve. The results showed that the pain threshold of sciatic nerve injury of rats was significantly reduced, and the expression level of P2×4 receptor in the spinal cord was significantly increased. While olfactory ensheathing cells combined with chitosan (OECs+CS) transplantation could significantly relieve pain, and the analgesic effect was stronger than that of OECs transplantation alone. OECs+CS transplantation promoted the formation of sciatic nerve remyelination, improved the changes of demyelination, and promoted the repair of sciatic nerve injury more significantly. In addition, the effect of OECs+CS to down-regulate the expression of P2×4 receptor was significantly stronger than that of OECs transplantation, and exerted a better analgesic effect. These data reveal that OECs+CS have a better analgesic effect in relieving neuropathic pain induced by sciatic nerve injury, and provide a new therapeutic strategy for pain treatment.

Role and therapeutic target of P2X2/3 receptors in visceral pain.

Visceral pain (VP) is caused by internal organ disease. VP is involved in nerve conduction and related signaling molecules, but its specific pathogenesis has not yet been fully elucidated. Currently, there are no effective methods for treating VP. The role of P2X2/3 in VP has progressed. After visceral organs are subjected to noxious stimulation, cells release ATP, activate P2X2/3, enhance the sensitivity of peripheral receptors and the plasticity of neurons, enhance sensory information transmission, sensitize the central nervous system, and play an important role in the development of VP. However, antagonists possess the pharmacological effect of relieving pain. Therefore, in this review, we summarize the biological functions of P2X2/3 and discuss the intrinsic link between P2X2/3 and VP. Moreover, we focus on the pharmacological effects of P2X2/3 antagonists on VP therapy and provide a theoretical basis for its targeted therapy.

Quantified versus willful handgrip exercises for the prevention of PICC-related thrombosis: A meta-analysis and systematic review.

BACKGROUND: Thrombosis is a common yet serious complication in patients with peripherally inserted central venous catheter (PICC), the prevention of thrombosis is very important to the prognosis of PICC patients. We aimed to evaluate the effects of quantified versus willful grip exercises for the prevention of PICC-related thrombosis, to provide evidence to the clinical nursing care of PICC patients. METHODS: Two authors searched PubMed et al databases for randomized controlled trials (RCTs) comparing the effects of quantified versus willful grip exercises in PICC patients up to August 31, 2022. Quality assessment and data extraction were independently performed by 2 researchers, and meta-analysis was performed using RevMan 5.3 software. RESULTS: 15 RCTs involving 1741 PICC patients were finally included in this meta-analysis. Synthesized outcomes indicated that compared with willful grip exercises, quantified grip exercises reduced the incidence of PICC-related thrombosis (odds ratio = 0.19, 95% confidence interval [CI]: 0.12-0.31) and infection (odds ratio = 0.30, 95% CI: 0.15-0.60) in PICC patients, increased the maximum venous velocity (mean difference = 3.02, 95% CI: 1.87-4.17) and mean blood flow (mean difference = 3.10, 95%CI: 1.57-4.62) in PICC patients (all P < .05). There were no publication biases amongst the synthesized outcomes (all P > .05). CONCLUSION: Quantified grip exercises can effectively reduce the occurrence of PICC-related thrombosis and infection, improve the venous hemodynamics. Limited by study population and regions, large-sample, and high-quality RCTs are still needed in the future to further evaluate the effects and safety of quantified grip exercises in PICC patients.

AKT/GSK-3beta/VEGF signaling is involved in P2RY2 activation-induced the proliferation and metastasis of gastric cancer.

Studies have revealed the contribution of ATP-G-protein-coupled P2Y2 receptor (P2RY2) in tumor progression, but the role of P2RY2 in regulating the progression of gastric cancer (GC) and related molecular mechanisms are relatively lacking. Therefore, this study investigates the effects of P2RY2 on the proliferation and migration of GC through in vivo and in vitro experiments. The results showed that P2RY2 was expressed in GC tissues and GC cell lines. Adenosine triphosphate (ATP) increased the calcium influx in AGS and HGC-27 cells, and was dose-dependent with ATP concentration. ATP and UTP increased the intracellular glycogen content, enhanced the actin fiber stress response, and promoted the proliferation and migration of GC cells, while P2RY2 competitive antagonist AR-C118925XX reversed the changes induced by ATP. Knockdown of P2RY2 expression by shRNA inhibited the proliferation of GC cells. Activation of P2RY2 increased the expression of Snail, Vimentin, and ß-catenin in GC cells, and down-regulated the expression of E-cadherin, while AR-C118925XX decreased the expression of these genes induced by ATP. Activation of P2RY2 activated AKT/GSK-3beta/VEGF signal to promote the proliferation of GC cells, and the P13/AKT signaling pathway LY294002 reversed the corresponding phenomenon, but no synergistic pharmacological properties of AR-C118925XX and LY294002 have been found. In vivo experiments showed that ATP-induced tumor growth, while AR-C118925XX inhibited ATP-induced tumor growth. Our conclusion is that P2RY2 activated the AKT/GSK-3beta/VEGF signal to promote the proliferation and migration of GC, suggesting that P2RY2 may be a new potential target for the treatment of GC.