The association between RAPSN methylation in peripheral blood and breast cancer in the Chinese population

Lei, Shuifang; Li, Lixi; Yang, Xiaoqin; Yin, Qiming; Tian, Xu; Zhou, Wenjie; Gu, Wanjian; Ma, Fei; Yang, Rongxi

doi:10.1038/s10038-021-00933-x

Cited by 4 publications

(3 citation statements)

References 44 publications

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“…Our data revealed that DNA methylation was related to the clinical characteristics of BC, consistent with our previous studies ( Lei et al, 2021 ; Yin et al, 2022 ). Here we found significantly lower methylation of CD160 , ISYNA1 and RAD51B were correlated with hormone receptor status, increased breast tumor size, advanced tumor stage and more lymph node involvement.…”

Section: Discussionsupporting

confidence: 92%

The Association Between Breast Cancer and Blood-Based Methylation of CD160, ISYNA1 and RAD51B in the Chinese Population

et al. 2022

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Recent studies have identified DNA methylation signatures in the white blood cells as potential biomarkers for breast cancer (BC) in the European population. Here, we investigated the association between BC and blood-based methylation of cluster of differentiation 160 (CD160), inositol-3-phosphate synthase 1 (ISYNA1) and RAD51 paralog B (RAD51B) genes in the Chinese population. Peripheral blood samples were collected from two independent case-control studies with a total of 272 sporadic early-stage BC cases (76.5% at stage I&II) and 272 cancer-free female controls. Mass spectrometry was applied to quantitatively measure the levels of DNA methylation. The logistic regression and non-parametric tests were used for the statistical analyses. In contrast to the protective effects reported in European women, we reported the blood-based hypomethylation in CD160, ISYNA1 and RAD51B as risk factors for BC in the Chinese population (CD160_CpG_3, CD160_CpG_4/cg20975414, ISYNA1_CpG_2, RAD51B_CpG_3 and RAD51B_CpG_4; odds ratios (ORs) per -10% methylation ranging from 1.08 to 1.67, p < 0.05 for all). Moreover, hypomethylation of CD160, ISYNA1 and RAD51B was significantly correlated with age, BC subtypes including estrogen receptor (ER)-negative BC tumors, triple negative tumors, BC cases with larger size, advanced stages and more lymph node involvement. Our results supported the report in European women that BC is associated with altered methylation of CD160, ISYNA1 and RAD51B in the peripheral blood, although the effects are opposite in the Chinese population. The difference between the two populations may be due to variant genetic background or life styles, implicating that the validations of epigenetic biomarkers in variant ethnic groups are warranted.

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Section: Discussionsupporting

confidence: 92%

The Association Between Breast Cancer and Blood-Based Methylation of CD160, ISYNA1 and RAD51B in the Chinese Population

et al. 2022

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“…The study demonstrated that macrophages, fibroblasts, and tumor cells all could release S100A4 into the tumor microenvironment ( 77 ), and its elevated concentration promoted the formation of a pre-metastatic niche ( 78 , 79 ). Several studies revealed an association between RAPSNT hypomethylation in the peripheral blood of different populations and breast and lung cancer ( 51 , 52 , 80 ).…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg1 as a promising adjuvant agent for enhancing the anti-cancer functions of granulocytes inhibited by noradrenaline

Zhu

Chen

et al. 2023

Front. Immunol.

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IntroductionIn recent years, numerous studies have confirmed that chronic stress is closely related to the development of cancer. Our previous research showed that high levels of stress hormones secreted in the body during chronic stress could inhibit the cancer-killing activity of granulocytes, which could further promote the development of cancer. Therefore, reversing the immunosuppressive effect of stress hormones on granulocytes is an urgent problem in clinical cancer treatment. Here, we selected noradrenaline (NA) as a representative stress hormone.Methods and resultsAfter screening many traditional Chinese herbal medicine active ingredients, a promising compound, ginsenoside Rg1, attracted our attention. We verified the immunoprotective effect of ginsenoside Rg1 on granulocytes in vitro and ex vivo, and attempted to understand its potential immunoprotective mechanism. We confirmed the immunoprotective effect of ginsenoside Rg1 on granulocytes using cell and animal experiments. Cell counting kit-8 (CCK-8) and ex vivo experiments were performed to investigate the immunoprotective effects of ginsenoside Rg1 on the anti-cancer function of granulocytes inhibited by NA. Transcriptome sequencing analysis and qRT-PCR showed that NA elevated the mRNA expression of ARG2, MMP1, S100A4, and RAPSN in granulocytes, thereby reducing the anti-cancer function of granulocytes. In contrast, ginsenoside Rg1 downregulated the mRNA expression of ARG2, MMP1, S100A4, and RAPSN, and upregulated the mRNA expression of LAMC2, DSC2, KRT6A, and FOSB, thereby enhancing the anti-cancer function of granulocytes inhibited by NA. Transwell cell migration experiments were performed to verify that ginsenoside Rg1 significantly enhanced the migration capability of granulocytes inhibited by NA. Tumor-bearing model mice were used to verify the significant immunoprotective effects in vivo. Finally, CCK-8 and hematoxylin and eosin staining experiments indicated that ginsenoside Rg1 exhibited high biosafety in vitro and in vivo.DiscussionIn future clinical treatments, ginsenoside Rg1 may be used as an adjuvant agent for cancer treatment to alleviate chronic stress-induced adverse events in cancer patients.

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“…The fact that RAPSN was the only transcript increased in expression by Insulin in this system is interesting. While RAPSN is mostly associated with developmental disorders of the neuronal system, more recently it has been identified as a potential biomarker for epithelial cell tumours including lung ( Qiao et al 2020 ) and breast ( Lei et al 2021 ). This could suggest a potential role in cellular proliferation – particularly given its role in the regulation of actin filaments ( Howe et al 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional response of endometrial cells to insulin, cultured using microfluidics

Baik

Maini

Tinning

et al. 2023

Reproduction and Fertility

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Obesity is a rapidly growing public health issue among women of reproductive age associated with decreased reproductive function including implantation failure. This can result from a myriad of factors including impaired gametes and endometrial dysfunction. The mechanisms of how obesity-related hyperinsulinaemia disrupts endometrial function are poorly understood. We investigated potential mechanisms by which insulin alters endometrial transcript expression. Ishikawa cells were seeded into a microfluidics device attached to a syringe pump to deliver a constant flow rate of 1uL/min of the following: 1) control 2) vehicle control (acetic acid) or, 3) Insulin (10 ng/ml) for 24 hours (n=3 biological replicates). Insulin-induced transcriptomic response of endometrial epithelial cells was determined via RNA sequencing, and DAVID and Webgestalt to identify Gene Ontology (GO) terms and signalling pathways. A Total of 29 transcripts showed differential expression levels across two comparison groups (control v vehicle control; vehicle control v insulin). Nine transcripts were differentially expressed in vehicle control v insulin comparison (p<0.05). Functional annotation analysis of transcripts altered by insulin (n=9) identified three significantly enriched GO terms: SRP-dependent cotranslational protein targeting to membrane, poly(A) binding, and RNA binding (p<0.05). Over-representation analysis found three significantly enriched signalling pathways relating to insulin-induced transcriptomic response: protein export, glutathione metabolism, and ribosome pathways (p<0.05). Transfection of siRNA for RASPN successfully knocked down expression (p<0.05) but this did not have any effect on cellular morphology. Insulin-induced dysregulation of biological functions and pathways highlight potential mechanisms by which high insulin concentrations within maternal circulation may perturb endometrial receptivity.

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The association between RAPSN methylation in peripheral blood and breast cancer in the Chinese population

Cited by 4 publications

References 44 publications

The Association Between Breast Cancer and Blood-Based Methylation of CD160, ISYNA1 and RAD51B in the Chinese Population

The Association Between Breast Cancer and Blood-Based Methylation of CD160, ISYNA1 and RAD51B in the Chinese Population

Ginsenoside Rg1 as a promising adjuvant agent for enhancing the anti-cancer functions of granulocytes inhibited by noradrenaline

Transcriptional response of endometrial cells to insulin, cultured using microfluidics

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