HTR3A is correlated with unfavorable histology and promotes proliferation through ERK phosphorylation in lung adenocarcinoma

Tone, Mitsuyo; Tahara, Shinichiro; Nojima, Satoshi; Motooka, Daisuke; Okuzaki, Daisuke; Morii, Eiichi

doi:10.1111/cas.14592

Cited by 11 publications

(13 citation statements)

References 15 publications

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“…Serotonin controls tumor growth by stimulating angiogenesis via modulation of the MMP12/angiostatin axis 101 . Lung adenocarcinoma is also known to express 5-HTR 3A, and knockdown of this receptor reduces the proliferation of lung adenocarcinoma cells 106 . Liu et al showed a negative correlation between 5-HTR 1A and 5-HTR 1B expression in lung adenocarcinoma tumors in patients with depression, and the number of tumor-specific T cells as well as the ratio of CD8/CD4 T cells present in the TME.…”

Section: Lung Cancermentioning

confidence: 99%

Role of serotonin receptor signaling in cancer cells and anti-tumor immunity

Karmakar

Lal

2021

Theranostics

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Serotonin or 5-hydroxytryptamine (5-HT) is a neurotransmitter known to affect emotion, behavior, and cognition, and its effects are mostly studied in neurological diseases. The crosstalk between the immune cells and the nervous system through serotonin and its receptors (5-HTRs) in the tumor microenvironment and the secondary lymphoid organs are known to affect cancer pathogenesis. However, the molecular mechanism of - alteration in the phenotype and function of - innate and adaptive immune cells by serotonin is not well explored. In this review, we discuss how serotonin and serotonin receptors modulate the phenotype and function of various immune cells, and how the 5-HT-5-HTR axis modulates antitumor immunity. Understanding how 5-HT and immune signaling are involved in tumor immunity could help improve therapeutic strategies to control cancer progression and metastasis.

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Section: Lung Cancermentioning

confidence: 99%

Role of serotonin receptor signaling in cancer cells and anti-tumor immunity

Karmakar

Lal

2021

Theranostics

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“…HTR3A has been demonstrated to participate in various biological processes, such as organismal energy homeostasis, interneuron migration and arrhythmias ( 33 – 35 ). Several recent papers have discussed the effects of HTR3A on tumor cells, which plays a role in tumor progression in specific types of cancer ( 36 , 37 ). For example, Tone et al.…”

Section: Discussionmentioning

confidence: 99%

“…For example, Tone et al. found that higher HTR3A expression was significantly associated with pathological stage, lymph node metastasis, lymphovascular invasion and recurrence in lung adenocarcinoma and further suggested that HTR3A promotes the aggressiveness of lung adenocarcinoma through ERK1/2 phosphorylation ( 36 ). Tang et al.…”

Section: Discussionmentioning

confidence: 99%

Construction of a Tumor Immune Microenvironment-Related Prognostic Model in BRAF-Mutated Papillary Thyroid Cancer

Xia

Jiang²,

Huang³

et al. 2022

Front. Endocrinol.

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BRAF mutation is a representative oncogenic mutation, with a frequency of 60% in papillary thyroid carcinoma (PTC), but the reasons for the poor prognosis and more aggressive course of BRAF-mutated PTC are controversial. Tumor immune microenvironment (TIME) is an essential factor permitting the development and progression of malignancy, but whether TIME participates in the prognosis of BRAF-mutated PTC has not yet been reported. The primary goal of the present study was to provide a comprehensive TIME-related prognostic model to increase the predictive accuracy of progression-free survival (PFS) in patients with BRAF-mutated PTC. In this study, we analyzed the mRNA-seq data and corresponding clinical data of PTC patients obtained from the TCGA database. By calculating the TIME scores (immune score, stromal score and ESTIMATE score), the BRAF mutation group (n=237) was dichotomized into the high- and low-score groups. By functional analysis of differentially expressed genes (DEGs) in different high/low score groups, we identified 2 key TIME-related genes, HTR3A and NIPAL4, which affected PFS in BRAF-mutated PTC. A risk scoring system was developed by multivariate Cox analysis based on the abovementioned 2 TIME-related genes. Then, the BRAF-mutated cohort was divided into the high- and low-risk groups using the median risk score as a cutoff. A high risk score correlated positively with a higher HTR3A/NIPAL4 expression level but negatively with PFS in BRAF-mutated PTC. Ultimately, a nomogram was constructed by combining risk score with clinical parameter (Tumor stage), and the areas under the ROC curve (AUCs) of the nomogram for predicting 1-, 3- and 5-year PFS were then calculated and found to be 0.694, 0.707 and 0.738, respectively, indicating the improved accuracy and clinical utility of the nomogram versus the risk score model in the BRAF-mutated PTC cohort. Moreover, we determined the associations between prognostic genes or risk score and immune cell infiltration by two-way ANOVA. In the high-risk score, high HTR3A expression, and high NIPAL4 expression groups, higher infiltration of immune cells was found. Collectively, these findings confirm that the nomogram is effective in predicting the outcome of BRAF-mutated PTC and will add a spatial dimension to the developing risk stratification system.

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“…The mortality of mechanically ventilated patients is high at 30% 1,2 . It has been suggested that 5‐hydroxytryptamine (5‐HT) plays a role in the pathophysiology of a wide range of diseases and conditions, including chronic obstructive pulmonary disease (COPD), 3,4 myocardial infarction, 5 adult respiratory distress syndrome, 6 sepsis, 7 lung ischemia–reperfusion injury, 8 pulmonary arterial hypertension, 9–12 interstitial lung diseases, 13 non‐small‐cell lung cancer and lung adenocarcinoma 14–16 . 5‐HT is an inflammatory mediator released in the lung 17 .…”

Section: Introductionmentioning

confidence: 99%

“…(5-HT) plays a role in the pathophysiology of a wide range of diseases and conditions, including chronic obstructive pulmonary disease (COPD), 3,4 myocardial infarction, 5 adult respiratory distress syndrome, 6 sepsis, 7 lung ischemia-reperfusion injury, 8 pulmonary arterial hypertension, [9][10][11][12] interstitial lung diseases, 13 non-small-cell lung cancer and lung adenocarcinoma. [14][15][16] 5-HT is an inflammatory mediator released in the lung. 17 Neuroepithelial bodies in the mammalian lung express the type-3 receptor of 5-HT.…”

mentioning

confidence: 99%

Mediators of neutrophil–lymphocyte ratio in the relationship between ondansetron pre‐treatment and the mortality of ICU patients on mechanical ventilation: Causal mediation analysis from the MIMIC‐IV database

Zhou

Tao

Zhang

et al. 2022

Brit J Clinical Pharma

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Aims The mortality of critically ill patients undergoing mechanical ventilation (MV) is high and few strategies are available. We explored the relationship between ondansetron pre‐treatment, the neutrophil–lymphocyte ratio (NLR), and platelet–lymphocyte ratio (PLR), and mortality of ventilated patients in the intensive care unit. Methods We developed a retrospective cohort study that involved patients undergoing MV in the Multiparameter Intelligent Monitoring in Intensive Care IV (MIMIC‐IV) database. Causal mediation analysis was conducted to assess the relationship of ondansetron use and mortality and to explore the potential causal pathway mediated by the NLR or PLR. The primary outcome was 28‐day mortality. Results A total of 17 927 eligible patients took part in the study (5665 had taken ondansetron before MV initiation and 12 262 patients had not). The odds ratio (OR) for 28‐day mortality for ondansetron use uncorrelated with the mediator (NLR, PLR) was 0.72 (95% confidence interval [CI] = 0.64–0.81, P < .001). Ondansetron was also associated with a reduction in 28‐day mortality after controlling for the mediator of NLR (OR = 0.98, 95% CI = 0.97–0.99, P < .01). For the indirect effect, the NLR could explain 13.47% (95% CI = 8.59–20.54%, P < .01) of the impact of ondansetron use on 28‐day mortality. The proportion mediated increased to 21.50% (95% CI = 12.36–47.44%, P < .01) for 90‐day mortality. Adjusted mediation analysis revealed no suggestion of a causal mediation pathway for this effect by the PLR (P = .12). Conclusions NLR may play substantial roles in the relationship between ondansetron pre‐treatment before initiation of mechanical ventilation and the reduction of death risk in ventilated patients.

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HTR3A is correlated with unfavorable histology and promotes proliferation through ERK phosphorylation in lung adenocarcinoma

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 11 publications

References 15 publications

Role of serotonin receptor signaling in cancer cells and anti-tumor immunity

Role of serotonin receptor signaling in cancer cells and anti-tumor immunity

Construction of a Tumor Immune Microenvironment-Related Prognostic Model in BRAF-Mutated Papillary Thyroid Cancer

Mediators of neutrophil–lymphocyte ratio in the relationship between ondansetron pre‐treatment and the mortality of ICU patients on mechanical ventilation: Causal mediation analysis from the MIMIC‐IV database

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