Cholinergic Receptor Nicotinic Alpha 5 (CHRNA5) RNAi is associated with cell cycle inhibition, apoptosis, DNA damage response and drug sensitivity in breast cancer

Koker, Sahika Cingir; Jahja, Ermira; Shehwana, Huma; Keşküş, Ayşe Gökçe; Konu, Özlen

doi:10.1371/journal.pone.0208982

Cited by 14 publications

(7 citation statements)

References 91 publications

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“…CpG site-annotated genes such as SAPCD2 are critical in the progression of cancers and cardiovascular diseases [ 39 ]. A previous report suggested that CHRNA5 RNAi was associated with cell cycle inhibition, apoptosis, reduced DNA damage response, and increased drug sensitivity in breast cancer [ 40 ]. CHRNA5 (15q25.1) is localized in lung cancer susceptibility loci, and CHRNA5 polymorphism is related to lung cancer susceptibility [ 41 , 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

Gene signature to predict prognostic survival of hepatocellular carcinoma

Cao

Fan

et al. 2022

Open Medicine

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Hepatocellular carcinoma (HCC) has a high incidence and poor prognosis and is the second most fatal cancer, and certain HCC patients also show high heterogeneity. This study developed a prognostic model for predicting clinical outcomes of HCC. RNA and microRNA (miRNA) sequencing data of HCC were obtained from the cancer genome atlas. RNA dysregulation between HCC tumors and adjacent normal liver tissues was examined by DESeq algorithms. Survival analysis was conducted to determine the basic prognostic indicators. We identified competing endogenous RNA (ceRNA) containing 15,364 pairs of mRNA–long noncoding RNA (lncRNA). An imbalanced ceRNA network comprising 8 miRNAs, 434 mRNAs, and 81 lncRNAs was developed using hypergeometric test. Functional analysis showed that these RNAs were closely associated with biosynthesis. Notably, 53 mRNAs showed a significant prognostic correlation. The least absolute shrinkage and selection operator’s feature selection detected four characteristic genes (SAPCD2, DKC1, CHRNA5, and UROD), based on which a four-gene independent prognostic signature for HCC was constructed using Cox regression analysis. The four-gene signature could stratify samples in the training, test, and external validation sets (p <0.01). Five-year survival area under ROC curve (AUC) in the training and validation sets was greater than 0.74. The current prognostic gene model exhibited a high stability and accuracy in predicting the overall survival (OS) of HCC patients.

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Section: Discussionmentioning

confidence: 99%

Gene signature to predict prognostic survival of hepatocellular carcinoma

Cao

Fan

et al. 2022

Open Medicine

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“…Furthermore, as α4β2α5 nicotinic receptors support higher conductance of calcium ions into the cell (Scholze & Huck, 2020; Sciaccaluga et al, 2015), another putative neuroprotective mechanism of the α5 subunit may be through driving possible calcium-dependent pro-survival pathways in the neurons which express the α4β2α5 nicotinic receptors (Cingir Koker et al, 2018; Ueda et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

CHRNA5links chandelier cells to severity of amyloid pathology in aging and Alzheimer’s Disease

Rybnicek

Chen

Milic

et al. 2022

Preprint

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Changes in high-affinity nicotinic acetylcholine receptors are intricately connected to cognitive impairment in Alzheimer's Disease (AD). While preclinical work suggests a possible protective and cognitive-enhancing role for the auxiliary nicotinic α5 subunit, mRNA expression of the CHRNA5 gene has not been closely examined in the context of human aging and dementia. Here, we investigate the impact of two common SNPs predicted to have different effects on the nicotinic α5 subunit: the function-compromising rs16969968 and the expression-altering rs1979905. We analyzed data from human prefrontal cortex (922 subjects with matched genotypic and post-mortem RNA sequencing, including 22 subjects with single-nucleus data) of elderly participants in the Religious Orders Study and Memory and Aging Project (ROS/MAP). We tested the impact of SNP haplotypes on prefrontal expression of CHRNA5 as well as that of SNPs in its receptor partners: CHRNA4 and CHRNB2. In the context of cognition and neuropathology, we observed a significant negative association between the high CHRNA5-expressing rs1979905A2 genotype and β-amyloid load in the prefrontal cortex. Our analyses revealed that the greatest abundance of CHRNA5 expression was in chandelier neurons, a sparse but disproportionately-powerful set of interneurons, in addition to layer 5 and 6 pyramidal neurons. In subjects with functionally-unaltered CHRNA5, the proportion of chandelier cells in the prefrontal cortex shows resilience to β-amyloid load, but this resilience is diminished in subjects homozygous for the minor allele of the CHRNA5 missense SNP rs16969968. Taken together, these findings urge further investigation into the role of CHRNA5 and chandelier cells in AD neuroprotection.

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“…The expression profile of nAChR subunits is different in subtypes of breast cancer [ 12 ]. The nAChRα5 associates with cell cycle, apoptosis, and DNA damage response of luminal-type breast cancer cells [ 13 ]. The nAChRα7 promotes cell proliferation and apoptosis in a panel of breast cancer cell lines [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…The expression levels of nAChR subunits are different on breast cancer cell lines [ 12 ]. It is reported that nicotine acts on breast cancer cells such as luminal- and TNBC-type via some nAChRs [ 13 – 21 ]. However, the nicotine-mediated biological effects including the regulation of immune-check point molecules on HER2-type breast cancer cells are largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Nicotine treatment regulates PD-L1 and PD-L2 expression via inhibition of Akt pathway in HER2-type breast cancer cells

et al. 2022

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The immune checkpoint molecules such as PD-L1 and PD-L2 have a substantial contribution to cancer immunotherapy including breast cancer. Microarray expression profiling identified several molecular subtypes, namely luminal-type (with a good-prognosis), HER2-type (with an intermediate-prognosis), and triple-negative breast cancer (TNBC)-type (with a poor-prognosis). We found that PD-L1 and PD-L2 mRNA expressions were highly expressed in TNBC-type cell lines (HCC1937, MDA-MB-231), moderately expressed in HER2-type cell line (SK-BR-3), and poorly expressed in luminal-type cell lines (MDA-MB-361, MCF7). The PD-L1 and PD-L2 expression in SK-BR-3 cells, but not those in HCC1937 and MDA-MB-231 cells, decreased by nicotine stimulation in a dose-dependent manner. In addition, nicotine treatment decreased the phosphorylation of Akt in SK-BR-3 cells, but not in other cell lines. These results show that nicotine regulates the expression of immune checkpoint molecules, PD-L1 and PD-L2, via inhibition of Akt phosphorylation. This findings may provide the new therapeutic strategies for the treatment of breast cancer.

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Cholinergic Receptor Nicotinic Alpha 5 (CHRNA5) RNAi is associated with cell cycle inhibition, apoptosis, DNA damage response and drug sensitivity in breast cancer

Cited by 14 publications

References 91 publications

Gene signature to predict prognostic survival of hepatocellular carcinoma

Gene signature to predict prognostic survival of hepatocellular carcinoma

CHRNA5links chandelier cells to severity of amyloid pathology in aging and Alzheimer’s Disease

Nicotine treatment regulates PD-L1 and PD-L2 expression via inhibition of Akt pathway in HER2-type breast cancer cells

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