Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan 50612, Korea.
BK21Plus Project, School of Dentistry, Pusan National University, Yangsan 50612, Korea.
Int J Mol Sci. 2020 Sep 30;21(19):7232. doi: 10.3390/ijms21197232.
Recent comparative studies have indicated distinct expression profiles of short, non-coding microRNAs (miRNAs) in various types of cancer, including oral squamous cell carcinoma (OSCC). In this study, we employed a hybrid approach using as well as OSCC cell lines to validate putative targets of oral cancer-related miRNAs both in vivo and in vitro. Following overexpression of miR-31, we found a significant decrease in the size of the imaginal wing discs and downregulation of a subset of putative targets, including (), an important regulator of the Wnt signaling pathway. Parallel experiments performed in OSCC cells have also confirmed a similar miR-31-dependent regulation of human that was not initially predicted as targets of human miR-31. Furthermore, we found subsequent downregulation of and , two of the main transcriptional targets of Wnt signaling, suggesting a potential role of miR-31 in regulating the cell cycle and proliferation of OSCC cells. Taken together, our -based in vivo system in conjunction with the human in vitro platform will thus provide a novel insight into a mammal-to--to-mammal approach to validate putative targets of human miRNA and to better understand the miRNA-target relationships that play an important role in the pathophysiology of oral cancer.
最近的比较研究表明,短的非编码 microRNAs(miRNAs)在各种类型的癌症中,包括口腔鳞状细胞癌(OSCC),具有独特的表达谱。在这项研究中,我们采用杂交方法,使用 和 OSCC 细胞系,在体内和体外验证与口腔癌相关的 miRNA 的潜在靶标。在过表达 miR-31 后,我们发现 的 翅盘大小显著减小,并且一组假定的靶标(包括 )下调,这是 Wnt 信号通路的重要调节剂。在 OSCC 细胞中进行的平行实验也证实了类似的 miR-31 依赖性调节人 ,这最初并未预测为人 miR-31 的靶标。此外,我们发现随后 Wnt 信号的两个主要转录靶标 和 下调,提示 miR-31 可能在调节 OSCC 细胞的细胞周期和增殖中发挥作用。总之,我们基于 的体内系统与人类体外平台相结合,将为验证人类 miRNA 的潜在靶标并更好地理解在口腔癌病理生理学中起重要作用的 miRNA-靶标关系提供新的见解。