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基于表达分析和生物信息学方法探讨 lncRNAs DUXAP8、LINC00963 和 FOXD2-AS1 在腔面型乳腺癌中的潜在作用。

The potential roles of lncRNAs DUXAP8, LINC00963, and FOXD2-AS1 in luminal breast cancer based on expression analysis and bioinformatic approaches.

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

Hum Cell. 2021 Jul;34(4):1227-1243. doi: 10.1007/s13577-021-00539-7. Epub 2021 May 27.

Abstract

Numerous studies have demonstrated that lncRNAs participate in regulatory networks of different cancers. Dysregulation of various lncRNAs such as DUXAP8, LINC00963, and FOXD2-AS1 has been reported in the development of various cancers. The aim of this study was investigation of the importance and potential roles of DUXAP8, LINC00963, and FOXD2-AS1 in ER breast cancer (BC). We examined the expression levels of DUXAP8, LINC00963, and FOXD2-AS1 in 71 luminal A and B tumor tissues and two luminal A cell lines (MCF7 and T47D) compared with adjacent non-tumor tissues and MCF10A cell line by qRT-PCR assay, respectively. For identifying the relation between three lncRNAs and luminal BC, bioinformatic analyses were performed using some databases and software including GENEVESTIGATOR software, GEPIA2, DAVID, REVIGO, STRING, lncATLAS, Kaplan-Meier plotter, starBase, and miRNet tool. The results showed the significant upregulation of all three lncRNAs in luminal A and B tumor specimens and cell lines. Upregulation of DUXAP8 and FOXD2-AS1 was significantly associated with progesterone receptor-positive (PR) and p53 protein expression in luminal BC patients, respectively. Based on bioinformatic analyses, DUXAP8 can be considered as a prognostic biomarker for patients with luminal BC. DUXAP8, LINC00963, and FOXD2-AS1 are involved in several cancer-associated signaling pathways and multiple cancer-related processes. In addition, bioinformatic analyses indicated that LINC00963/hsa-mir-130a-3p/HSPA8 axis might have potential regulatory role in BC. In conclusion, dysregulation of DUXAP8, LINC00963, and FOXD2-AS1 can play roles in the development of luminal BC. They may exert their functions through involvement in some cancer signaling pathways and processes. In addition, they may interact with miRNAs like predicted interaction of LINC00963 with miR-130a-3p.

摘要

大量研究表明,lncRNAs 参与了不同癌症的调控网络。在各种癌症的发展过程中,已经报道了各种 lncRNAs(如 DUXAP8、LINC00963 和 FOXD2-AS1)的失调。本研究旨在探讨 DUXAP8、LINC00963 和 FOXD2-AS1 在 ER 乳腺癌(BC)中的重要性和潜在作用。我们通过 qRT-PCR 检测了 71 例 luminal A 和 B 肿瘤组织和两种 luminal A 细胞系(MCF7 和 T47D)中 DUXAP8、LINC00963 和 FOXD2-AS1 的表达水平,与相邻非肿瘤组织和 MCF10A 细胞系进行了比较。为了确定这三种 lncRNAs 与 luminal BC 的关系,我们使用了一些数据库和软件进行了生物信息学分析,包括 GENEVESTIGATOR 软件、GEPIA2、DAVID、REVIGO、STRING、lncATLAS、Kaplan-Meier plotter、starBase 和 miRNet 工具。结果表明,这三种 lncRNAs 在 luminal A 和 B 肿瘤标本和细胞系中均显著上调。在 luminal BC 患者中,DUXAP8 和 FOXD2-AS1 的上调与孕激素受体阳性(PR)和 p53 蛋白表达显著相关。基于生物信息学分析,DUXAP8 可以被认为是 luminal BC 患者的预后生物标志物。DUXAP8、LINC00963 和 FOXD2-AS1 参与了几种癌症相关的信号通路和多个与癌症相关的过程。此外,生物信息学分析表明,LINC00963/hsa-mir-130a-3p/HSPA8 轴可能在 BC 中具有潜在的调节作用。总之,DUXAP8、LINC00963 和 FOXD2-AS1 的失调可能在 luminal BC 的发生中发挥作用。它们可能通过参与一些癌症信号通路和过程来发挥作用。此外,它们可能与 miRNA 相互作用,如预测的 LINC00963 与 miR-130a-3p 的相互作用。

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