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The interaction between MALAT1 target, miR-143-3p, and RALGAPA2 is affected by functional SNP rs3827693 in breast cancer.
Human Cell ( IF 3.4 ) Pub Date : 2020-09-03 , DOI: 10.1007/s13577-020-00422-x
Nasrin Fattahi Dolatabadi 1 , Arezo Dehghani 1 , Elham Shahand 1 , Mohammadreza Yazdanshenas 1 , Hossein Tabatabaeian 2, 3 , Atefe Zamani 1 , Mansoureh Azadeh 1 , Kamran Ghaedi 2, 4
Affiliation  

A higher expression of MALAT1 has been reported in breast cancer. However, more studies are needed to decipher the mechanisms by which this lncRNA imposes its oncogenic effects. In this study, blood and tissue samples were taken from healthy normal and breast cancer subjects. qPCR was used to analyze the gene expression. HRM-PCR method was carried out to genotype the selected samples. Computational analysis was recruited to find novel targets of MALAT1 and miR-143-3p. The data analyses revealed that MALAT1 was up-regulated in breast cancer and could be a distinctive factor to diagnose cancer. The expression of MALAT1 was inversely correlated with miR-143-3p expression in the studied clinical samples. The down-regulation of miR-143-3p was proven in the clinical tumor samples as compared to the healthy controls. A negative correlation of miR-143-3p with its putative target, RALGAPA2 was observed. A functional SNP rs3827693 located within the 3′UTR region of RALGAPA2 mRNA was validated in this study to associate with breast cancer risk. The rs3827693 allele G significantly decreased the breast cancer incidence and augmented the negative correlation between RALGAPA2 and miR-143-3p, presumably through strengthening the interaction between these two transcripts. This study proposed MALAT1 miR-143-3p and miR-143-3p RALGAPA2 axis in breast cancer, whereby the latter can be altered by the clinically functional SNP rs3827693.



中文翻译:

MALAT1 靶标、miR-143-3p 和 RALGAPA2 之间的相互作用受乳腺癌中功能性 SNP rs3827693 的影响。

据报道,MALAT1 在乳腺癌中的表达更高。然而,需要更多的研究来破译这种 lncRNA 施加其致癌作用的机制。在这项研究中,血液和组织样本取自健康的正常人和乳腺癌受试者。qPCR用于分析基因表达。进行 HRM-PCR 方法对选定的样本进行基因分型。计算分析被招募来寻找 MALAT1 和 miR-143-3p 的新靶点。数据分析显示,MALAT1 在乳腺癌中上调,可能是诊断癌症的一个独特因素。在所研究的临床样本中,MALAT1 的表达与 miR-143-3p 的表达呈负相关。与健康对照相比,临床肿瘤样本中证实了 miR-143-3p 的下调。观察到 miR-143-3p 与其推定的靶标 RALGAPA2 呈负相关。本研究验证了位于 RALGAPA2 mRNA 3'UTR 区域内的功能性 SNP rs3827693 与乳腺癌风险相关。rs3827693 等位基因 G 显着降低了乳腺癌发病率并增强了 RALGAPA2 和 miR-143-3p 之间的负相关性,可能是通过加强这两个转录物之间的相互作用。该研究提出了乳腺癌中的 MALAT1 miR-143-3p 和 miR-143-3p RALGAPA2 轴,后者可以通过临床功能性 SNP rs3827693 改变。rs3827693 等位基因 G 显着降低了乳腺癌发病率并增强了 RALGAPA2 和 miR-143-3p 之间的负相关性,可能是通过加强这两个转录物之间的相互作用。该研究提出了乳腺癌中的 MALAT1 miR-143-3p 和 miR-143-3p RALGAPA2 轴,后者可以通过临床功能性 SNP rs3827693 改变。rs3827693 等位基因 G 显着降低了乳腺癌发病率并增强了 RALGAPA2 和 miR-143-3p 之间的负相关性,可能是通过加强这两个转录物之间的相互作用。该研究提出了乳腺癌中的 MALAT1 miR-143-3p 和 miR-143-3p RALGAPA2 轴,后者可以通过临床功能性 SNP rs3827693 改变。

更新日期:2020-09-03
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