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乳腺癌相关 GAS5 和 LSINCT5 lncRNAs 在无癌乳腺组织中的表达水平:与初潮年龄和肥胖的分子关联。

Expression levels of breast cancer-related GAS5 and LSINCT5 lncRNAs in cancer-free breast tissue: Molecular associations with age at menarche and obesity.

机构信息

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.

出版信息

Breast J. 2018 Nov;24(6):876-882. doi: 10.1111/tbj.13067. Epub 2018 May 21.

DOI:10.1111/tbj.13067
PMID:29785740
Abstract

Long noncoding RNAs (lncRNAs) constitute a major class of the human transcriptome which play crucial roles in the key biological processes of both normal and malignant breast cells. Although the aberrant expression of lncRNAs has been well-documented in breast cancer (BC), little is currently known about the association between their expression levels in the breast tissue of healthy women and BC risk factors, especially the reproductive or demographic characteristics that are among the most well-known BC risk modifiers. This study was an attempt to investigate the correlation between the expression levels of 2 breast cancer-related lncRNAs, including GAS5 and LSINCT5, and reproductive and demographic characteristics in 145 normal breast tissues that were obtained from women without breast cancer undergoing cosmetic surgery. Total RNA was extracted from fresh normal breast tissues, and the expression level of target lncRNAs was quantified using real-time qPCR. Differences in the mean normalized gene expression among the subgroups of different variables were analyzed. The expression levels of both genes was lower in the overweight-obese (BMI ≥ 25) subgroup than that in the normal BMI (BMI < 25) subgroup (GAS5 P = .019, LSINCT5 P = .036). Moreover, the expression level of GAS5 was negatively correlated with BMI (r: -.170, P: .041). The expression level of GAS5 was higher in women with late menarche (>13 years) than that with early menarche (≤13 years; P = .017). These findings may assist to obtain insights into the molecular mechanisms through which the reproductive or obesity-related estrogen changes contribute to the breast carcinogenesis. In conclusion, this study presents the first evidence for the presence of a link between the lncRNA expression and the reproductive or obesity related factors in the breast tissue of healthy women.

摘要

长链非编码 RNA(lncRNA)构成了人类转录组的主要类别,在正常和恶性乳腺细胞的关键生物学过程中发挥着至关重要的作用。尽管 lncRNA 的异常表达在乳腺癌(BC)中已有很好的记载,但目前对于健康女性乳腺组织中 lncRNA 表达水平与 BC 风险因素之间的关联知之甚少,尤其是那些作为最知名的 BC 风险修饰因子的生殖或人口统计学特征。本研究试图调查 2 种与乳腺癌相关的 lncRNA(包括 GAS5 和 LSINCT5)的表达水平与 145 例来自接受美容手术的无乳腺癌女性的正常乳腺组织中的生殖和人口统计学特征之间的相关性。从新鲜的正常乳腺组织中提取总 RNA,并使用实时 qPCR 定量测定靶标 lncRNA 的表达水平。分析不同变量亚组之间平均归一化基因表达的差异。超重肥胖(BMI≥25)亚组中两种基因的表达水平均低于正常 BMI(BMI<25)亚组(GAS5 P=.019,LSINCT5 P=.036)。此外,GAS5 的表达水平与 BMI 呈负相关(r:-.170,P:.041)。初潮较晚(>13 岁)的女性 GAS5 表达水平高于初潮较早(≤13 岁)的女性(P=.017)。这些发现可能有助于深入了解生殖或肥胖相关雌激素变化对乳腺癌发生的分子机制。总之,本研究首次证明了 lncRNA 表达与健康女性乳腺组织中的生殖或肥胖相关因素之间存在联系。

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