Downregulation of 5‑hydroxytryptamine receptor�3A expression exerts an anticancer activity against cell growth in colorectal carcinoma cells in�vitro

Tang, Jian; Wang, Zheng; Liu, Jiahua; Zhou, Chao; Chen, Jinxian

doi:10.3892/ol.2018.9351

Cited by 6 publications

(7 citation statements)

References 38 publications

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“…Tang et al. found that HTR3A may contribute to the development of colorectal carcinoma (CRC) and confirmed that the expression of some Bcl-2 family proteins, including BAX, BCL-2 and BAD proteins, was mainly regulated by HTR3A and participated in CRC cell cycle progression, cell proliferation and apoptosis ( 37 ). The present study confirmed that upregulation of HTR3A was associated with shorter PFS in BRAF-mutated PTC, supporting a tumor-promoting role of HTR3A and a potential role in predicting prognosis.…”

Section: Discussionmentioning

confidence: 94%

“…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%

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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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Section: Discussionmentioning

confidence: 94%

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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“…HTR3A is the main component of 5‐HT3 receptor. HTR3A or 5‐HT3 receptor is related to cancer progression in some types of cancer including lung carcinoma 6,7 . To date, no studies have compared HTR3A expression in histologic subtypes of lung adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…Lee et al 6 reported that 5‐HT3 receptor antagonists are related to antitumor mechanisms in lung cancer. Tang et al 7 reported that downregulation of HTR3A expression exerts an anticancer activity against cell growth in colorectal carcinoma cells. However, whether HTR3A correlates with histopathological findings, such as the histologic subtypes or the distribution in an individual sample, remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…It has been reported that 5-HT is a key mediator of the growth of colon carcinoma allografts in vivo [104]. Studies on 5-HT receptor 3A (HTR3A) knockdown in the six CCc lines showed inhibition of their proliferation and colony formation, resulting in cell cycle arrest and the promotion of cell apoptosis [105]. Other studies confirm the role of serotonin and its receptors (5-HT(1B), 5-HT(3), 5-HT(4)) in enhancing CRC growth.…”

Section: Neurotransmitters (Nts)mentioning

confidence: 96%

The Neuropeptide System and Colorectal Cancer Liver Metastases: Mechanisms and Management

Kasprzak

Adamek

2020

IJMS

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Colorectal cancer (CRC), classified as the third most prevalent cancer worldwide, remains to be a clinical and research challenge. It is estimated that ~50% of CRC patients die from distant metastases, with treatment of this complication still posing significant difficulties. While liver metastasis (LM) cascade is known in the literature, its mechanisms are still unclear and remain studied in different research models. A connection is suggested between nervous system dysfunctions and a range of Neurotransmitters (Nts) (including Neuropeptides, NPs), Neurotrophins (Ntt) and their receptors (Rs) in CRC liver metastasis development. Studies on the role of NP/NP-Rs in the progression and metastasis of CRC, show the complexity of brain–tumor interactions, caused by their different forms of release to the extracellular environment (endocrine, autocrine, paracrine and neurocrine). Many stages of LM are connected to the activity of pro-inflammatory, e.g., Corticotropin-releasing Hormone Receptor 1 (CRHR1), Neuropeptide Y (NPY) and Neurotensin (NT), anti-inflammatory, e.g., Calcitonin Gene-related Peptide (CGRP), CRHR2 and Vasoactive Intestinal Polypeptide (VIP) or dual role neuropeptides, e.g., Substance P (SP). The regulation of the local immunological profile (e.g., CRH/CRHRs), dysfunctions of enteroprotective role of NPs on epithelial cells (e.g., NT/NT-R), as well as structural-functional changes in enteric nervous system innervation of the tumor are also important. More research is needed to understand the exact mechanisms of communication between the neurons and tumor cells. The knowledge on the mechanisms regulating tumor growth and different stages of metastasis, as well as effects of the action of a numerous group of Nts/NPs/Ntt as growth factors, have implications for future therapeutic strategies. To obtain the best treatment outcomes, it is important to use signaling pathways common for many NPs, as well to develop a range of broad-spectrum antagonists. This review aims to summarize the current knowledge on the importance of neuroactive molecules in the promotion of the invasion-metastasis cascade in CRC, as well as the improvements of clinical management of CRC liver metastasis.

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Downregulation of 5‑hydroxytryptamine receptor�3A expression exerts an anticancer activity against cell growth in colorectal carcinoma cells in�vitro

Cited by 6 publications

References 38 publications

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

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

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

The Neuropeptide System and Colorectal Cancer Liver Metastases: Mechanisms and Management

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