Darbeheshti Farzaneh, Zokaei Elham, Mansoori Yaser, Emadi Allahyari Sima, Kamaliyan Zeeba, Kadkhoda Sepideh, Tavakkoly Bazzaz Javad, Rezaei Nima, Shakoori Abbas
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Medical Genetics Network (MeGeNe), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
Cancer Cell Int. 2021 Jun 14;21(1):312. doi: 10.1186/s12935-021-02015-6.
Circular RNAs (circRNAs) have been implicated in the initiation and development of breast cancer as functional non-coding RNAs (ncRNA). The roles of circRNAs as the competing endogenous RNAs (ceRNAs) to sponge microRNAs (miRNAs) have also been indicated. However, the functions of circRNAs in breast cancer have not been totally elucidated. This study aimed to explore the clinical implications and possible roles of circ_0044234 in carcinogenesis of the most problematic BC subtype, triple negative breast cancer (TNBC), which are in desperate need of biomarkers and targeted therapies.
The importance of circ_0044234 as one of the most dysregulated circRNAs in TNBC was discovered through microarray expression profile analysis. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to confirm the downregulation of circ_0044234 in triple negative tumors and cell lines versus non-triple negative ones. The bioinformatics prediction revealed that circ_0044234 could act as an upstream sponge in the miR-135b/GATA3 axis, two of the most dysregulated transcripts in TNBC.
Our experimental investigation of circ_0044234 expressions in various BC subtypes as well as cell lines reveals that TNBC expresses circ_0044234 at a substantially lower level than non-TNBC. The ROC curve analysis indicates that it could be applied as a discriminative biomarker to identify TNBC from other BC subtypes. Moreover, circ_0044234 expression could be an independent prognostic biomarker in BC. Interestingly, a substantial inverse expression correlation was detected between circ_0044234 and miR-135b-5p as well as between miR-135b-5p and GATA3 in breast tumors.
The possible clinical usefulness of circ_0044234 as a promising distinct biomarker and upcoming therapeutic target for TNBC have been indicated in this research. Our comprehensive approach revealed the potential circ_0044234/miR135b-5p/GATA3 ceRNA axis in TNBC.
环状RNA（circRNAs）作为功能性非编码RNA（ncRNA），与乳腺癌的发生和发展有关。环状RNA作为竞争性内源RNA（ceRNAs）来海绵化微小RNA（miRNAs）的作用也已得到证实。然而，环状RNA在乳腺癌中的功能尚未完全阐明。本研究旨在探讨circ_0044234在最具问题的乳腺癌亚型——三阴性乳腺癌（TNBC）致癌过程中的临床意义及可能作用，而TNBC迫切需要生物标志物和靶向治疗。
通过微阵列表达谱分析发现circ_0044234作为TNBC中失调最严重的环状RNA之一的重要性。进行逆转录定量聚合酶链反应（RT-qPCR）以确认三阴性肿瘤和细胞系中circ_0044234相对于非三阴性肿瘤和细胞系的下调情况。生物信息学预测显示circ_0044234可能在miR-135b/GATA3轴中作为上游海绵发挥作用，miR-135b/GATA3是TNBC中失调最严重的两个转录本。
我们对circ_0044234在各种乳腺癌亚型以及细胞系中的表达进行的实验研究表明，TNBC中circ_0044234的表达水平明显低于非TNBC。ROC曲线分析表明，它可作为一种鉴别生物标志物，用于从其他乳腺癌亚型中识别TNBC。此外，circ_0044234的表达可能是乳腺癌中的一个独立预后生物标志物。有趣的是，在乳腺肿瘤中检测到circ_0044234与miR-135b-5p之间以及miR-135b-5p与GATA3之间存在显著的反向表达相关性。
本研究表明circ_0044234作为TNBC一种有前景的独特生物标志物和未来治疗靶点可能具有的临床实用性。我们全面的研究方法揭示了TNBC中潜在的circ_0044234/miR135b-5p/GATA3 ceRNA轴。
