Peng Ningning, Miao Zhigang, Wang Liguo, Liu Binbin, Wang Guijiang, Guo Xu
Department of Orthopedics, Cangzhou Central Hospital, Hebei Medical University, Cangzhou, 061000, Hebei, China.
Biochem Cell Biol. 2018 Oct;96(5):515-521. doi: 10.1139/bcb-2017-0186. Epub 2018 Feb 28.
MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in a variety of biological processes. Dysregulation of miRNAs is tightly associated with the malignancy of cancers. Aberrant expression of miR-378 has been observed in human cancers; however, the function of miR-378 in osteosarcoma (OS) remains largely unknown. Here, we showed that miR-378 was highly expressed in human OS tissues and cell lines. Overexpression of miR-378 significantly promoted the cell proliferation of OS cells. Molecular studies identified Kruppel-like factor-9 (KLF9) as a functional downstream target of miR-378. MiR-378 directly bound to the mRNA 3'-UTR region of KLF9 and suppressed the expression of KLF9. Highly expressed KLF9 reversed the promoting effect of miR-378 on the proliferation of OS cells. The expression level of miR-378 was negatively correlated with that of KLF9 in OS tissues. Collectively, our results demonstrated the molecular interaction between miR-378 and KLF9, indicating the therapeutic potential of miR-378 for OS.
微小RNA(miRNA)是一类小的非编码RNA,在多种生物学过程中发挥重要作用。miRNA的失调与癌症的恶性程度密切相关。在人类癌症中已观察到miR-378的异常表达;然而,miR-378在骨肉瘤(OS)中的功能仍 largely 未知。在此,我们表明miR-378在人类OS组织和细胞系中高表达。miR-378的过表达显著促进了OS细胞的增殖。分子研究确定Kruppel样因子9(KLF9)是miR-378的功能性下游靶标。miR-378直接结合到KLF9的mRNA 3'-UTR区域并抑制KLF9的表达。高表达的KLF9逆转了miR-378对OS细胞增殖的促进作用。在OS组织中,miR-378的表达水平与KLF9的表达水平呈负相关。总体而言,我们的结果证明了miR-378与KLF9之间的分子相互作用,表明miR-378对OS具有治疗潜力。