{"title":"The role of G protein-coupled receptor 4 in inflammatory diseases and its potential clinical significance.","authors":"Qilimuge Bai, Gegentuya Bao, Yali Yan, Saqirina Hereid, Xiaohong Bai, Liang Bao","doi":"10.1080/10799893.2025.2529174","DOIUrl":"10.1080/10799893.2025.2529174","url":null,"abstract":"<p><p>G protein-coupled receptor 4 (GPR4) is a dual ligand receptor that can be activated by both protons and lysophosphatidylcholine (LPC), which is a bioactive phospholipid. It plays a pivotal role in numerous physiological and pathological processes and is regulated by these two ligands through distinct mechanisms. Recently, there has been growing interest in the role of GPR4 in diseases characterized by an acidic microenvironment. This review aims to explore the specific signaling pathways through which protons and LPC regulate GPR4 in the inflammatory microenvironment and to clarify the distinct roles of these ligands in various diseases, including inflammation, atherosclerosis, and cancer. Additionally, the potential benefits and challenges of targeting GPR4 as a therapeutic strategy for these diseases are analyzed.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"214-219"},"PeriodicalIF":2.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ahmad Tarmizi Che Has, Fatin H Mohamad, Muhammad Zulfadhli Othman, Khairul Bariyyah Abd Halim
{"title":"Paradoxical action of zolpidem: interplay between dysregulation of the synergetic actions of γ-aminobutyric acid type A receptors and neuronal cotransporters (KCC2/NKCC1).","authors":"Ahmad Tarmizi Che Has, Fatin H Mohamad, Muhammad Zulfadhli Othman, Khairul Bariyyah Abd Halim","doi":"10.1080/10799893.2025.2530105","DOIUrl":"10.1080/10799893.2025.2530105","url":null,"abstract":"<p><p>Zolpidem, or commercially known as Ambien or Stilnox, is a sedative-hypnotic agent, which is usually prescribed to manage sleeping difficulties in individuals with insomnia. The site of its sedative-hypnotic action is the γ-aminobutyric acid type A receptor, which it shares with benzodiazepines. However, this substance has been consistently associated to awaken patients with brain injuries such as trauma, stroke, disorders of consciousness and has also been expanded to the recovery of brain function in the event of hypoxic damage, cerebrovascular ischemic injury, infection of the central nervous system, toxins and poisoning, degenerative diseases, tumors, and congenital disorders. Aside from that, the effect has been observed in a wide spectrum of neurological diseases, from movement disorders such as Parkinson's disease and dystonia to neurological deficits and anaphylactic hypoxia. The wide spectrum of injuries and disorders reported poses a challenge in investigating the exact mechanisms of action underlying the awakening effect. Therefore, the main question is how it is possible for a substance originally intended as a sedative-hypnotic agent to induce an awakening effect? In this review, we discuss the synergetic roles of GABA<sub>A</sub> receptors, which are the target receptor for zolpidem, along with neuronal cation-Cl<sup>-</sup> co-transporters KCC2/NKCC1 in regulating the inhibitory nature of the GABAergic transmission in brain injury, which might explain the awakening effect of zolpidem in brain injuries.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"220-229"},"PeriodicalIF":2.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A novel anticancer candidate, coumarin-3-carboxamide derivative inhibits cell proliferation and migration in MDA-MB-231 cell line.","authors":"Sevide Sencan, Hulya Celik Onar","doi":"10.1080/10799893.2025.2513696","DOIUrl":"10.1080/10799893.2025.2513696","url":null,"abstract":"<p><p>Breast cancer is one of the leading cancer types in terms of morbidity and mortality worldwide. Although developing technology, early diagnosis and treatment opportunities provide positive contributions to the treatment of breast cancer, research on new drugs that are less toxic to healthy cells, safer and more effective for cancer cells, increasing the quality of life of the patient is still ongoing. Coumarin and its derivatives have been shown great interest to develop safer and more effective anticancer drugs. Therefore, we investigated the anticancer activity of novel coumarin-3-carboxamide derivative 3i in MDA-MB-231 cells. We found that coumarin-3-carboxamide derivative 3i inhibited cell proliferation, colony formation and migration. However, coumarin-3-carboxamide derivative 3i did not induce apoptosis and autophagy. Consequently, our findings suggest for the first time that novel coumarin-3-carboxamide 3i has anticancer activity and may be an important drug candidate for the treatment of triple-negative breast cancer. Further investigations are required to elucidate its impact on breast cancer.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"230-236"},"PeriodicalIF":2.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Karoliny Nune Santos, Juliana Q Bizzotto, Thainá O Bueno-Pereira, Mariana Romao-Veiga, Vanessa R Ribeiro-Vasques, Larissa Ragozo Cardoso Oliveira, Valéria C Sandrim, Priscila R Nunes
{"title":"Preeclamptic plasma disrupts endothelial function and promotes inflammation in endothelial cells: beneficial effects of glibenclamide and MCC950 in this scenario.","authors":"Karoliny Nune Santos, Juliana Q Bizzotto, Thainá O Bueno-Pereira, Mariana Romao-Veiga, Vanessa R Ribeiro-Vasques, Larissa Ragozo Cardoso Oliveira, Valéria C Sandrim, Priscila R Nunes","doi":"10.1080/10799893.2025.2535579","DOIUrl":"10.1080/10799893.2025.2535579","url":null,"abstract":"<p><p>Preeclampsia (PE) is characterized by systemic endothelial dysfunction and remains a significant clinical challenge. Activation of NLRP3 inflammasome, reactive oxygen species (ROS) production, and pyroptosis and autophagy are important mechanisms in this condition. To evaluate the NLRP3 inhibitors effects: glibenclamide (GB) and MCC950, on markers of inflammation, endothelial dysfunction, cell death, and oxidative stress in an <i>in vitro</i> model of PE. Plasma from pregnant women with PE and normotensive pregnant women (NT) was used to investigate its impact on NLRP3 inflammasome activation (NLRP3, TLR4, MyD88, and caspase-1) in endothelial cells (ECs), analyzed by Western Blotting; effects of pharmacological inhibition on the function of ECs was assessed by the evaluation of permeability (VE-cadherin) and markers of endothelial dysfunction by flow cytometry (Flt-1, VEGFR2, E-selectin, VCAM-1, and ICAM-1), as well as cytotoxicity measured by lactate dehydrogenase (LDH), oxidative stress (ROS, nitric oxide - NO and antioxidant capacity), autophagy, and pyroptosis (interleukin IL-1β and high-mobility group box one - HMGB1). Both GB and MCC950 reduced NLRP3 inflammasome activation and its related effects in ECs exposed to PE plasma, including lowered IL-1β, caspase-1, modulated adhesion molecules expression, as well as decreased ROS and cytotoxicity. GB increased NO and restored VE-cadherin expression, while MCC950 enhanced antioxidant capacity. GB also induced autophagy, unlike MCC950. The NLRP3 inhibitors showed the potential to mitigate endothelial dysfunction, oxidative stress, and inflammation, suggesting both compounds hold potential therapeutic value for PE through distinct mechanisms.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"237-249"},"PeriodicalIF":2.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meilan Su, Yuan Chang, Xiaoting Wu, Qinglin Wang, Song Wang
{"title":"N-methyl-d-aspartate receptor is involved in the progression of anxiety disorders with thyroid tumors.","authors":"Meilan Su, Yuan Chang, Xiaoting Wu, Qinglin Wang, Song Wang","doi":"10.1080/10799893.2025.2540309","DOIUrl":"https://doi.org/10.1080/10799893.2025.2540309","url":null,"abstract":"<p><strong>Background: </strong>Anxiety disorders (ADs) and thyroid tumors (TTs) are prevalent and frequently co-occur. Previous studies suggest that the N-methyl-d-aspartate receptor (NMDAR) may play a role in their co-occurrence, but the understanding of their relationship is not comprehensive. The aim of this study was to investigate the role of NMDAR in the progression of animal models of AD with TT.</p><p><strong>Methods: </strong>We developed an animal model of AD with TT in Balb/c mice using chronic unpredictable mild stress (CUMS) combined with subcutaneous IHH4 cell xenotransplantation. Mice were treated with d-serine and MK-801 to assess behavioral changes and tumor growth. The expression of NMDAR subunits in the thyroid and transplanted TT tissues was also analyzed.</p><p><strong>Results: </strong>The combination of CUMS and IHH4 cell xenotransplantation helped successfully create an AD with TT model, which exhibited stable anxiety-like behavior, a high tumor formation rate, and ease of implementation. d-Serine alleviated anxiety behaviors but increased NR2A subunit activity in both thyroid and TT tissues, disrupted the normal structure of the thyroid, and accelerated TT growth. In contrast, MK-801 had the opposite effect.</p><p><strong>Conclusions: </strong>NMDAR, particularly the NR2A subunit, plays a crucial role in TT progression associated with AD. In the clinical drug selection for the patients with ADs with concomitant TT, special attention should be paid to the two-sidedness of drugs. The CUMS and IHH4 xenotransplantation model is an effective tool for studying AD with TT.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"1-10"},"PeriodicalIF":2.3,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aysel Kalayci Yigin, Ali Azzawri, Kayhan Ozturk, Tulin Cora, Mehmet Seven
{"title":"Determination of cytokine profile and associated genes of the signaling pathway in HNSCC.","authors":"Aysel Kalayci Yigin, Ali Azzawri, Kayhan Ozturk, Tulin Cora, Mehmet Seven","doi":"10.1080/10799893.2021.2013888","DOIUrl":"https://doi.org/10.1080/10799893.2021.2013888","url":null,"abstract":"<p><p>Head and neck squamose cell carcinoma (HNSCC) is an aggressive group of tumors that are generally heterogeneous. Despite treatment advances, disease-free survival has not significantly improved. Therefore, it is of great importance to understand the molecular etiology of HNSCC and genetic alterations in the signal pathways in order to develop new therapeutic approaches. In this study, firstly we used a cytokine array to analyze the secretomes of HNSCC patients and healthy controls. In the next step, the results from the cytokine sequence were validated by qRT-PCR and western blot, including genes in the associated signaling pathway. In array analysis, the levels of EGF, IGF-1, IGFBP-1, and PDGFBB were significantly higher in patients than in the controls. The results of qRT-PCR analyses showed that expression levels of <i>PDGFRB</i> gene were significantly up-regulated (<i>p</i> = 0.006) and <i>PTEN</i> (<i>p</i> > 0.001) were significantly down-regulated in tumors compared with normal tissues. When groups (early vs. advanced) were compared, higher expression of <i>IGFBP-1</i> was observed in the larynx (<i>p</i> = 0.045) and larynx + oral cavity tumors (<i>p</i> = 0.010) in an advanced stage. In western blot analysis, pEGFR, pIGF-IR, pIR-β, pPDGFRB, and pAKT levels were upregulated, and pPTEN was downregulated in tumors. Based on our observations, determining the interactions of <i>EGFR, PDGFRB, IGF-1R</i> and <i>PTEN</i> or the activation of each might represent a promising new and innovative treatment approach in HNSCC patients. It seems clear that, in most cancers, effective targeted therapy may be involved the blockade of each one or multiple targets.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"462-468"},"PeriodicalIF":2.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39821902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vinutha Kuchana, Vaeshnavi Kashetti, Sai Kiran Reddy Peddi, Sreekanth Sivan, Vijjulatha Manga
{"title":"Integrated computational approach for <i>in silico</i> design of new purinyl pyridine derivatives as B-Raf kinase inhibitors.","authors":"Vinutha Kuchana, Vaeshnavi Kashetti, Sai Kiran Reddy Peddi, Sreekanth Sivan, Vijjulatha Manga","doi":"10.1080/10799893.2021.1999472","DOIUrl":"https://doi.org/10.1080/10799893.2021.1999472","url":null,"abstract":"<p><p>B-Raf is one among the most frequently mutating proto-oncogene which is associated with the serine/threonine Raf kinase family involved in the RAS-RAF-MEK-ERK pathway, which is the most deregulated pathway in human cancers. Mutant B-Raf <sup>V600E</sup> got an excellent scope for investigation in cancer as a potential therapeutic target. Formerly B-Raf<sup>V600E</sup> is considered the molecular target for numerous antitumor compounds like purinyl pyridine and pyrimidine derivatives. In the current research work using molecular docking approach of Schrodinger Glide 5.6 version, ligand docking, pharmacophore-based virtual screening, binding free energy calculations of a series of 2-amino purinyl pyridine and pyrimidine derivatives were modeled, their docking values were predicted, that were considered to be potent against B-Raf <sup>V600E</sup>. A five-point hypothesis accompanied by a hydrogen bond acceptor(A), two hydrogen bond donors(D), and two aromatic rings (R) was built with a justifiable R<sup>2</sup> value of 0.91 and a Q<sup>2</sup> value of 0.64. Then by using Asinex Elite Synergy database, virtual screening was performed, and identified several potential hits. Subsequently, the molecules which had interactions with the target B-Raf kinase were determined by subjecting the obtained hits for SP and XP docking processes. Finally, for the top leads obtained, binding free energies were accomplished. About 16 new purinyl pyridine molecules were also designed. Almost nine molecules manifested crucial ligand interactions and binding free energies. At the outset, this research paved the way for us in spotting new molecules with B-Raf inhibitory activity, which can further be explored to design molecules with enhanced pharmacokinetic profiles.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"439-453"},"PeriodicalIF":2.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39677280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Target-based in-silico screening of basil polysaccharides against different epigenetic targets responsible for breast cancer.","authors":"Nancy Bhura, Pawan Gupta, Jeena Gupta","doi":"10.1080/10799893.2022.2058016","DOIUrl":"https://doi.org/10.1080/10799893.2022.2058016","url":null,"abstract":"<p><strong>Purpose: </strong>Breast cancer (BC) is one of the leading types of cancer found in women. One of the causes reported for BC is improper regulation of epigenetic modifications. Various epigenetic targets such as histone deacetylases (HDAC) and histone acetyltransferases (HAT) regulate many types of cancer, including BC. Basil is known to possess anti-cancer properties; however, the role of its polysaccharides against different epigenetic targets is still not very clear. Therefore, the molecular docking method is used to find out the binding potential of the BPSs against different epigenetic targets responsible for BC.</p><p><strong>Methods: </strong>All the basil polysaccharides (BPSs) were screened against the diverse epigenetic targets reported for BC (HDAC1-2, 4-8, and HAT) using molecular docking studies alongwith swissADME studies to check the drug likeliness of the BPSs.</p><p><strong>Results: </strong>It was found that glucosamine ring, glucosamine linear, glucuronic acid linear, rhamnose linear, glucuronic acid ring, galactose ring, mannose, glucose, and xylose were exhibited consistent binding potential against the epigenetic targets (HDAC1, HDAC2, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, and HAT,) responsible for BC.</p><p><strong>Conclusion: </strong>This is the first report where BPSs were reported against these epigenetic targets. These studies can help to understand the underlying mechanism of BPSs used against epigenetic targets for BC. These results can be further validated experimentally to confirm their potential as a promising inhibitor against the epigenetic targets (HDAC1-2, 4-8, and HAT) having a role in BC.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"521-530"},"PeriodicalIF":2.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40610971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hassan Ghasemi, Ali Jamshidi, Mohammad Amin Ghatee, Komeil Mazhab-Jafari, Milad Khorasani, Mina Rahmati, Saeed Mohammadi
{"title":"PPARγ activation by pioglitazone enhances the anti-proliferative effects of doxorubicin on pro-monocytic THP-1 leukemia cells via inducing apoptosis and G2/M cell cycle arrest.","authors":"Hassan Ghasemi, Ali Jamshidi, Mohammad Amin Ghatee, Komeil Mazhab-Jafari, Milad Khorasani, Mina Rahmati, Saeed Mohammadi","doi":"10.1080/10799893.2021.1988972","DOIUrl":"https://doi.org/10.1080/10799893.2021.1988972","url":null,"abstract":"<p><strong>Purpose: </strong>Doxorubicin (DOX) is a common chemotherapeutic agent, with toxic side effects, and chemoresistance. Combination chemotherapy is a successful approach to overcome these limitations. Here, we investigated the effects of pioglitazone (PGZ), a PPARγ agonist, and/or DOX on the viability, cell cycle, apoptosis on THP-1 cells and normal human monocytes (NHMs).</p><p><strong>Methods: </strong>MTT assay was used to evaluate the cytotoxicity of DOX and/or PGZ. Cell cycle progression and apoptosis induction were examined by PI or Annexin V-PI double staining, and analyzed by flow cytometry. Quantitative RT-PCR was used to evaluate the changes in the mRNA expression of cell cycle progression or apoptosis-associated genes including P27, P21, CDK2, P53, BCL2 and FasR.</p><p><strong>Results: </strong>DOX, PGZ and DOX + PGZ exerted their cytotoxic effects in a dose- and time-dependent manner with low toxicity on NHMs. The cell growth inhibitory effects of DOX were in association with G2/M arrest, while PGZ executed S phase arrest. PGZ treatment enhanced G2/M among DOX-treated combinations with moderate elevation in the S phase. DOX, PGZ and combined treatments induced apoptosis (mostly late phase) in a dose-dependent manner. All treatments resulted in the significant overexpression of p21, p27, p53 and FasR genes and downregulation of CDK2. DOX + PGZ combined treatments exhibited the most significant changes in mRNA expression.</p><p><strong>Conclusion: </strong>We demonstrated that the antiproliferative, cell cycle regulation and apoptosis-inducing capacity of DOX was enhanced by PGZ in THP-1 leukemia cells in a dose-dependent manner. Therefore, the combination of DOX + PGZ could be used as a novel combination to target AML.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"429-438"},"PeriodicalIF":2.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39514651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jing Li, Liyan Che, Chang Xu, Dongdong Lu, Yan Xu, Mengru Liu, Wenshu Chai
{"title":"XIST/miR-34a-5p/PDL1 axis regulated the development of lung cancer cells and the immune function of CD8<sup>+</sup> T cells.","authors":"Jing Li, Liyan Che, Chang Xu, Dongdong Lu, Yan Xu, Mengru Liu, Wenshu Chai","doi":"10.1080/10799893.2021.2019274","DOIUrl":"https://doi.org/10.1080/10799893.2021.2019274","url":null,"abstract":"<p><strong>Purpose: </strong>Long non-coding RNA (lncRNA) XIST has been shown to be involved in the immune escape of breast cancer, but it is unclear whether it is involved in the immune escape of lung cancer, so it will be discussed in this study.</p><p><strong>Methods: </strong>XIST and miR-34a-5p expression in lung cancer tissues and cells were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The targeting relationship between miR-34a-5p and XIST/programmed cell death receptor ligand 1 (PDL1) was predicted by bioinformatics website and verified by dual-luciferase report experiment. After co-transfection with XIST specific short hairpin RNA (sh-XIST) and miR-34a-5p inhibitors, the changes in PDL1 expression, and cell biological behavior were detected by qRT-PCR, cell counting kit 8, flow cytometry, and Transwell experiments. Similarly, after co-transfection of PDL1 specific small interfering RNA (siPDL1) and miR-34a-5p inhibitors, the changes in cell biological behavior were detected again. After CD8+ T cells were co-cultured with lung cancer cells transfected with sh-XIST and miR-34a-5p inhibitors, the expression of cytokines and immunosuppressive molecules was detected by western blot and enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>XIST was up-regulated in lung cancer tissues, while miR-34a-5p was the opposite. XIST up-regulated the expression of PDL1 by targeting miR-34a-5p, thereby affecting the viability, apoptosis, migration, and invasion of lung cancer cells. In the co-culture system, XIST targeted miR-34a-5p to inhibit cytokines secretion and promote the expression of immunosuppressive molecules.</p><p><strong>Conclusions: </strong>XIST/miR-34a-5p/PDL1 axis was involved in the malignant biological behavior of lung cancer cells and the immune function of CD8<sup>+</sup> T cells.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"469-478"},"PeriodicalIF":2.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39850416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}