Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Medical Genetic Ward, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
J Transl Med. 2021 Aug 26;19(1):364. doi: 10.1186/s12967-021-03026-7.
Luminal breast cancer (BC) is the most frequent subtype accounting for more than 70% of BC. LncRNAs, a class of non-coding RNAs with more than 200 nucleotides, are involved in a variety of cellular processes and biological functions. Abberant expression is related to the development of various cancers, such as breast cancer. LINC01133, ZEB1-AS1, and ABHD11-AS1 were reported to be dysregulated in different cancers. However, their expression level in luminal BC remains poorly known. The aim of the present study was to evaluate the potential roles of these lncRNAs in BC, especially in luminal subtypes.
A comprehensive analysis was performed using the Lnc2Cancer database to identify novel cancer-associated lncRNA candidates. After conducting a literature review, three novel lncRNAs named LINC01133, ZEB1-AS1, and ABHD11-AS1 were chosen as target genes of the present study. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to evaluate the expression level of the mentioned lncRNAs in both luminal BC tissues and cell lines. Then, the correlation of the three mentioned lncRNAs expression with clinicopathological characteristics of the patients was studied. Moreover, several datasets were used to discover the potential roles and functions of LINC01133, ZEB1-AS1 and ABHD11-AS1 in luminal subtype of BC.
According to the qRT-PCR assay, the expression levels of LINC01133 and ZEB1-AS1 were decreased in luminal BC tissues and cell lines. On the other hand, ABHD11-AS1 was upregulated in the above-mentioned samples. The expression levels of LINC01133, ZEB1-AS1, and ABHD11-AS1 were not associated with any of the clinical features. Also, the results obtained from the bioinformatics analyses were consistent with qRT-PCR data. Functional annotation of the co-expressed genes with the target lncRNAs, protein-protein interactions and significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways across luminal BC were also obtained using bioinformatics analysis.
Taken together, our findings disclosed the dysregulation of LINC01133, ZEB1-AS1, and ABHD11-AS1 in luminal BC. It was revealed that LINC01133 and ZEB1-AS1 expression was significantly downregulated in luminal BC tissues and cell lines, while ABHD11-AS1 was upregulated considerably in the mentioned tissues and cell lines. Also, bioinformatics and systems biology analyses have helped to identify the possible role of these lncRNAs in luminal BC. However, further analysis is needed to confirm the current findings.
腔腺癌（BC）是最常见的亚型，占 BC 的 70%以上。长非编码 RNA（lncRNA）是一类具有超过 200 个核苷酸的非编码 RNA，参与多种细胞过程和生物功能。异常表达与包括乳腺癌在内的各种癌症的发展有关。据报道，LINC01133、ZEB1-AS1 和 ABHD11-AS1 在不同的癌症中存在失调。然而，它们在腔腺癌中的表达水平仍知之甚少。本研究的目的是评估这些 lncRNA 在 BC 中的潜在作用，特别是在腔型中的作用。
使用 Lnc2Cancer 数据库进行综合分析，以确定新的癌症相关 lncRNA 候选物。通过文献回顾，选择了三个新的 lncRNA，命名为 LINC01133、ZEB1-AS1 和 ABHD11-AS1，作为本研究的靶基因。采用实时定量聚合酶链反应（qRT-PCR）评估了所述 lncRNA 在腔腺癌组织和细胞系中的表达水平。然后，研究了这三种 lncRNA 的表达与患者临床病理特征的相关性。此外，还使用了多个数据集来发现 LINC01133、ZEB1-AS1 和 ABHD11-AS1 在腔型 BC 中的潜在作用和功能。
根据 qRT-PCR 检测，LINC01133 和 ZEB1-AS1 的表达水平在腔腺癌组织和细胞系中降低，而 ABHD11-AS1 的表达水平升高。LINC01133、ZEB1-AS1 和 ABHD11-AS1 的表达水平与任何临床特征均无关联。此外，生物信息学分析得到的结果与 qRT-PCR 数据一致。通过生物信息学分析还获得了与靶 lncRNA 共表达的基因、蛋白质-蛋白质相互作用以及腔型 BC 中显著富集的京都基因与基因组百科全书（KEGG）途径的功能注释。
综上所述，本研究揭示了 LINC01133、ZEB1-AS1 和 ABHD11-AS1 在腔腺癌中的失调。结果表明，LINC01133 和 ZEB1-AS1 在腔腺癌组织和细胞系中的表达显著下调，而 ABHD11-AS1 在上述组织和细胞系中显著上调。此外，生物信息学和系统生物学分析有助于确定这些 lncRNA 在腔腺癌中的可能作用。然而，需要进一步的分析来证实目前的发现。
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