Department of Pathophysiology, School of Basic Medical Science, Central South University, Changsha, China.
Department of Gynaecology, the Affiliated Zhuzhou Hospital Xiangya Medical College, Central South University, Zhuzhou, China.
J Cell Mol Med. 2021 Apr;25(7):3327-3338. doi: 10.1111/jcmm.16402. Epub 2021 Feb 26.
MicroRNAs (miRNAs) are widely distributed in cells and participate in the regulation of the pathophysiological process of many diseases. As an important part of non-coding RNA, miRNAs regulate a variety of molecules and signal pathways in tumour cells. However, the evidence for regulatory mechanisms of specific miRNAs in tumour cells is still lacking.
In this study, we used transcriptomics analysis and integrated a variety of public databases to screen miRNAs that have key regulatory effects on breast cancer (BC). In addition, we used in vitro and in vivo studies and combined clinical samples to verify its regulatory mechanism.
We found that among the specific miRNAs, miR-215-5p is a key regulator in BC. Compared with normal adjacent tissues, miR-215-5p has a lower expression level in BC tissues. Patients with high expression levels of miR-215-5p have a longer survival time. miR-215-5p can specifically target the 3'UTR region of RAD54B mRNA and down-regulate the expression of RAD54B, thereby inhibiting the proliferation of BC cells and promoting the apoptosis of BC cells.
Finally, we found that miR-215-5p can be used as an important biomarker for BC. We have clarified its function and revealed its mechanism of targeting RAD54B mRNA for the first time. This may provide important clues to reveal the deeper molecular regulation mechanism of BC.
MicroRNAs（miRNAs）广泛分布于细胞中，参与多种疾病的病理生理过程的调节。作为非编码 RNA 的重要组成部分，miRNAs 调节肿瘤细胞中的多种分子和信号通路。然而，特定 miRNA 在肿瘤细胞中调控机制的证据仍然缺乏。
本研究采用转录组学分析，并整合多种公共数据库，筛选对乳腺癌（BC）具有关键调控作用的 miRNAs。此外，我们使用体外和体内研究，并结合临床样本验证其调控机制。
我们发现，在特定的 miRNAs 中，miR-215-5p 是 BC 的关键调节因子。与正常相邻组织相比，BC 组织中 miR-215-5p 的表达水平较低。miR-215-5p 高表达的患者生存时间更长。miR-215-5p 可以特异性靶向 RAD54B mRNA 的 3'UTR 区域并下调 RAD54B 的表达，从而抑制 BC 细胞的增殖并促进 BC 细胞的凋亡。
最后，我们发现 miR-215-5p 可以作为 BC 的重要生物标志物。我们阐明了其功能，并首次揭示了其靶向 RAD54B mRNA 的机制。这可能为揭示 BC 更深层次的分子调控机制提供重要线索。
