Alpha5 Nicotinic Acetylcholine Receptor Contributes to Nicotine-Induced Lung Cancer Development and Progression

Sun, Hongchen; Jia, Yanfei

doi:10.3389/fphar.2017.00573

Cited by 38 publications

(39 citation statements)

References 49 publications

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“…As α5-nAChR expression was observed to be associated with Jab1 expression in lung cancer patient samples, we further assessed α5-nAChR and Jab1 expressions in NSCLC xenograft tissues. As we previously reported, 17 the tumour volumes of α5-nAChR knockdown xenografts (KD) were smaller than those of the xenografts derived from control cells (NC) (Figure 2A). The immunohistochemistry assay showed that the expression of α5-nAChR and Jab1 was higher in the NC group compared to that observed in the sh-CHRNA5 tumour group ( Figure 2B).…”

Section: α5-nachr and Jab1 Expressions Are Correlated In Nsclc Tumosupporting

confidence: 78%

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α5‐nAChR contributes to epithelial‐mesenchymal transition and metastasis by regulating Jab1/Csn5 signalling in lung cancer

Chen

Jia

Zhang

et al. 2020

J Cellular Molecular Medi

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Recent studies have showed that α5 nicotinic acetylcholine receptor (α5‐nAChR) is closely associated with nicotine‐related lung cancer. Our previous studies also demonstrated that α5‐nAChR mediates nicotine‐induced lung carcinogenesis. However, the mechanism by which α5‐nAChR functions in lung carcinogenesis remains to be elucidated. Jab1/Csn5 is a key regulatory factor in smoking‐induced lung cancer. In this study, we explored the underlying mechanisms linking the α5‐nAChR‐Jab1/Csn5 axis with lung cancer epithelial‐mesenchymal transition (EMT) and metastasis, which may provide potential therapeutic targets for future lung cancer treatments. Our results demonstrated that the expression of α5‐nAChR was correlated with the expression of Jab1/Csn5 in lung cancer tissues and lung cancer cells. α5‐nAChR expression is associated with Jab1/Csn5 expression in lung tumour xenografts in mice. In vitro, the expression of α5‐nAChR mediated Stat3 and Jab1/Csn5 expression, significantly regulating the expression of the EMT markers, N‐cadherin and Vimentin. In addition, the down‐regulation of α5‐nAChR or/and Stat3 reduced Jab1/Csn5 expression, while the silencing of α5‐nAChR or Jab1/Csn5 inhibited the migration and invasion of NSCLC cells. Mechanistically, α5‐nAChR contributes to EMT and metastasis by regulating Stat3‐Jab1/Csn5 signalling in NSCLC, suggesting that α5‐nAChR may be a potential target in NSCLC diagnosis and immunotherapy.

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Section: α5-nachr and Jab1 Expressions Are Correlated In Nsclc Tumosupporting

confidence: 78%

“…Recently, our laboratory demonstrated that α5-nAChR mediates nicotine-induced lung cancer development and progression. 17 Nicotine interacts with α5-nAChR on the cell surface, activating the JAK2/Stat3 signalling pathways and promoting lung cancer cell proliferation. 18 Furthermore, α5-nAChR mediates nicotine-induced lung cancer cell migration and invasion.…”

mentioning

confidence: 99%

α5‐nAChR contributes to epithelial‐mesenchymal transition and metastasis by regulating Jab1/Csn5 signalling in lung cancer

Chen

Jia

Zhang

et al. 2020

J Cellular Molecular Medi

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“…It will be particularly insightful for at least three lung diseases where smoking may partly impact homeostasis: lung cancers, COPD, and COVID-19. (i) nAChRs single nucleotide polymorphisms (SNP) were associated to lung cancer cells [36,37] and nAChRs were shown to be involved in cancer cell proliferation and survival [38][39][40][41]. (ii) nAChRs SNPs were also associated with nicotine dependence and COPD [42][43][44][45][46].…”

Section: Discussionmentioning

confidence: 99%

Nicotinic receptors atlas in the adult human lung

Diabasana

Perotin-Collard

Belgacemi

et al. 2020

Preprint

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ABSTRACTNicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels responsible for the rapid neural and neuromuscular signal transmission. Although it is well documented that 16 subunits are encoded by the human genome, their presence in airway epithelial cells (AEC) remains poorly understood, and contribution to pathology is mainly discussed in the context of cancer. We analysed nAChR subunit expression in the human lung of smokers and non-smokers using transcriptomic data for whole lung tissues, isolated large AEC, and isolated small AEC. We identified differential expressions of nAChRs in terms of detection and repartition in the three modalities. Smoking-associated alterations were also unveiled. Then, we identified a nAChR transcriptomic print at a single cell level. Finally, we reported the localizations of detectable nAChRs in bronchi and large bronchioles. Thus, we compiled the first complete atlas of pulmonary nAChRs to open new avenues to further unravel the involvement of these receptors in lung homeostasis and respiratory diseases.

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“…Single nucleotide polymorphisms (SNPs) in the cholinergic nicotinic receptor subunit genes on chromosome 15q25.1, including CHRNA3, CHRNB4, and CHRNA5, are well-established biomarkers of chronic obstructive pulmonary disease (COPD) and lung cancer [15]. Several polymorphisms and their haplotypes in CHRNA5/CHRNA3 genes may have functional effects on (i) CHRNA5 mRNA levels, (ii) polycyclic aromatic hydrocarbon-DNA adduct levels, (iii) TP53 mutations, and (iv) susceptibility to lung cancer [16]. However, the function of the nicotinic receptor cluster on chromosome 15q25 in LAC is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Expression and Prognostic Significance of the Nicotinic Receptor Cluster on 15q25 about CHRNA5 and PSMA4 mRNA in Lung Adenocarcinoma Utilizing TCGA Datasets

Wang

et al. 2020

Preprint

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Background: Genome-wide association studies of lung cancer have shown a common variation at 15q24-25.1 as a determinant of risk, but the role of specific genes has not been proven. This study aims to explore the expression of mutations and the prognostic significance of 15q25 (CHRNA5 and PSMA4) mRNA in lung adenocarcinoma (LAC) based on immunohistochemistry, TCGA and bioinformatics. Methods: The expression of mutations on chromosome 15q25 of 576 primary LAC patients was selected and survival and gene expression data were extracted from TCGA. The relationship between expression of genes on 15q25 and clinical and prognostic Significance of LAC. An experiment with Beas-2b, A549 and H1299 cell lines was performed to further prove the difference in CHRNA5 and PSMA4 expression between lung cancer and normal cells. Immunohistochemistry data of CHRNA5 and PSMA4 were detected in LAC and normal tissues from 122 patients. Finally, Gene enrichment analysis (GSEA) was conducted to predict the regulatory genes of CHRNA5 and PSMA4. Results: CHRNA5 and PSMA4 are frequently mutated in TCGA (CHRNA5, 1.7%; PSMA4, 1.3%). Besides, the expression of CHRNA5 and PSMA4 was obviously higher in A549 and H1299 cells. And the immunohistochemical staining revealed that the levels of CHRNA5 and PSMA4 were considerably higher in the LAC group than in the normal group. Meanwhile, there was a significant association between high CHRNA5 expression and smoking history (P=0.011), smoking history pack year value (P=0.010). Furthermore, there was a significant correlation between CHRNA5 and PSMA4 expression levels and prognosis (P=0.003; P=0.008), and between higher expression and worse prognosis. GSEA results suggested that between samples with high CHRNA5 and PSMA4 expression were respectively enriched to cell cycle, base excision repair, oxidative phosphorylation, protein export, and aminoacyl tRNA biosynthesis, among others. Conclusions: CHRNA5 and PSMA4 mRNA expression has a significant impact on the clinical and survival of LAC, and they may be a potential target for treating patients with lung adenocarcinoma.

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Alpha5 Nicotinic Acetylcholine Receptor Contributes to Nicotine-Induced Lung Cancer Development and Progression

Cited by 38 publications

References 49 publications

α5‐nAChR contributes to epithelial‐mesenchymal transition and metastasis by regulating Jab1/Csn5 signalling in lung cancer

α5‐nAChR contributes to epithelial‐mesenchymal transition and metastasis by regulating Jab1/Csn5 signalling in lung cancer

Nicotinic receptors atlas in the adult human lung

Expression and Prognostic Significance of the Nicotinic Receptor Cluster on 15q25 about CHRNA5 and PSMA4 mRNA in Lung Adenocarcinoma Utilizing TCGA Datasets

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