Xia Hongping, Qi Yanting, Ng Samuel S, Chen Xiaona, Li Dan, Chen Shen, Ge Ruiguang, Jiang Songshan, Li Guo, Chen Yangchao, He Ming-Liang, Kung Hsiang-fu, Lai Lihui, Lin Marie C
Integrative Chemical Biology Laboratory, Institute of Molecular Technology, Department of Chemistry, The University of Hong Kong, Pokfulam, Hong Kong, China.
Brain Res. 2009 May 7;1269:158-65. doi: 10.1016/j.brainres.2009.02.037. Epub 2009 Mar 3.
MicroRNAs (miRNAs) are a class of endogenous, small non-protein coding single-stranded RNA molecules, which are crucial post-transcriptional regulators of gene expression. Previous studies have shown that miRNAs participate in a wide range of biological functions and play important roles in various human diseases including glioma. However, the role of miRNAs in mediating glioblastoma cell migration and invasion has not been elucidated. Using miRNA microarray, we identified miR-146b as one of the miRNAs that is significantly dysregulated in human glioblastoma tissue. We showed that miR-146b overexpression by transfection with the precursor miR-146b, or knock-down by Locked Nucleic Acid (LNA)-modified anti-miR-146b, has no effect on the growth of human glioblastoma U373 cells. However, precursor miR-146b transfection significantly reduced the migration and invasion of U373 cells, while LNA-anti-miR-146b transfection generated the opposite result. Furthermore, we discovered that a matrix metalloproteinase gene, MMP16, is one of the downstream targets of miR-146b. Taken together, our findings suggest that miR-146b is involved in glioma cell migration and invasion by targeting MMPs, and implicate miR-146b as a metastasis-inhibiting miRNA in glioma.
微小RNA（miRNA）是一类内源性的、非蛋白质编码的小单链RNA分子，是基因表达至关重要的转录后调节因子。先前的研究表明，miRNA参与广泛的生物学功能，并在包括胶质瘤在内的各种人类疾病中发挥重要作用。然而，miRNA在介导胶质母细胞瘤细胞迁移和侵袭中的作用尚未阐明。通过miRNA微阵列，我们鉴定出miR-146b是在人类胶质母细胞瘤组织中显著失调的miRNA之一。我们发现，用前体miR-146b转染过表达miR-146b，或用锁核酸（LNA）修饰的抗miR-146b敲低，对人类胶质母细胞瘤U373细胞的生长没有影响。然而，前体miR-146b转染显著降低了U373细胞的迁移和侵袭，而LNA-抗miR-146b转染则产生相反的结果。此外，我们发现基质金属蛋白酶基因MMP16是miR-146b的下游靶点之一。综上所述，我们的研究结果表明，miR-146b通过靶向基质金属蛋白酶参与胶质瘤细胞的迁移和侵袭，并表明miR-146b是胶质瘤中的一种转移抑制性miRNA。
