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通过计算方法鉴定可能导致人类三阴性乳腺癌的长非编码 RNA 候选物。

Identification of Potential Long Non-Coding RNA Candidates that Contribute to Triple-Negative Breast Cancer in Humans through Computational Approach.

机构信息

Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi 6205, Bangladesh.

Department of Chemistry, Binghamton University, State University of New York, Vestal, New York, NY 13902, USA.

出版信息

Int J Mol Sci. 2021 Nov 16;22(22):12359. doi: 10.3390/ijms222212359.

Abstract

Breast cancer (BC) is the most frequent malignancy identified in adult females, resulting in enormous financial losses worldwide. Owing to the heterogeneity as well as various molecular subtypes, the molecular pathways underlying carcinogenesis in various forms of BC are distinct. Therefore, the advancement of alternative therapy is required to combat the ailment. Recent analyses propose that long non-coding RNAs (lncRNAs) perform an essential function in controlling immune response, and therefore, may provide essential information about the disorder. However, their function in patients with triple-negative BC (TNBC) has not been explored in detail. Here, we analyzed the changes in the genomic expression of messenger RNA (mRNA) and lncRNA in standard control in response to cancer metastasis using publicly available single-cell RNA-Seq data. We identified a total of 197 potentially novel lncRNAs in TNBC patients of which 86 were differentially upregulated and 111 were differentially downregulated. In addition, among the 909 candidate lncRNA transcripts, 19 were significantly differentially expressed (DE) of which three were upregulated and 16 were downregulated. On the other hand, 1901 mRNA transcripts were significantly DE of which 1110 were upregulated and 791 were downregulated by TNBCs subtypes. The Gene Ontology (GO) analyses showed that some of the host genes were enriched in various biological, molecular, and cellular functions. The Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis showed that some of the genes were involved in only one pathway of prostate cancer. The lncRNA-miRNA-gene network analysis showed that the lncRNAs TCONS_00076394 and TCONS_00051377 interacted with breast cancer-related micro RNAs (miRNAs) and the host genes of these lncRNAs were also functionally related to breast cancer. Thus, this study provides novel lncRNAs as potential biomarkers for the therapeutic intervention of this cancer subtype.

摘要

乳腺癌(BC)是成年女性中最常见的恶性肿瘤,在全球范围内造成了巨大的经济损失。由于异质性以及各种分子亚型,各种形式的 BC 致癌的分子途径是不同的。因此,需要开发替代疗法来对抗这种疾病。最近的分析表明,长非编码 RNA(lncRNA)在控制免疫反应中发挥着重要作用,因此,可能提供有关该疾病的重要信息。然而,它们在三阴性乳腺癌(TNBC)患者中的功能尚未详细探讨。在这里,我们使用公开的单细胞 RNA-Seq 数据分析了信使 RNA(mRNA)和 lncRNA 的基因组表达在标准对照中对癌症转移的变化。我们总共鉴定出 197 个潜在的新型 lncRNA 在 TNBC 患者中,其中 86 个上调,111 个下调。此外,在 909 个候选 lncRNA 转录本中,有 19 个显著差异表达(DE),其中 3 个上调,16 个下调。另一方面,1901 个 mRNA 转录本显著 DE,其中 1110 个上调,791 个下调。基因本体论(GO)分析表明,一些宿主基因在各种生物学、分子和细胞功能中富集。京都基因与基因组百科全书(KEGG)途径分析表明,一些基因仅参与一个前列腺癌途径。lncRNA-miRNA-gene 网络分析表明,lncRNAs TCONS_00076394 和 TCONS_00051377 与乳腺癌相关的 micro RNA(miRNA)相互作用,这些 lncRNA 的宿主基因也与乳腺癌功能相关。因此,这项研究提供了新的 lncRNA 作为治疗干预这种癌症亚型的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1571/8619140/b9e39fd60732/ijms-22-12359-g001.jpg

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