MicroRNA-16 inhibits glioma cell growth and invasion through suppression of BCL2 and the nuclear factor-κB1/MMP9 signaling pathway.
Bottom Line: MicroRNA-16 decreased glioma malignancy by downregulating NF-κB1 and MMP9, and led to suppressed invasiveness of human glioma cell lines SHG44, U87, and U373.Our results also indicated that upregulation of miR-16 promoted apoptosis by suppressing BCL2 expression.Finally, the upregulation of miR-16 in a nude mice model of human glioma resulted in significant suppression of glioma growth and invasiveness.
Affiliation: Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.Show MeSH
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Mentions: By analyzing the homology between miR-16 and NF-κB1 mRNA sequences, we observed that the 15 nucleotides from the 5′ end of miR-16 were complementary to bases 255–279 of the NF-κB1 cDNA (Homo sapiens, NM_003998 AK122850 M58603; Fig.2a). A dual-luciferase reporter assay system was used to validate whether miR-16 directly recognizes the 3′-UTR region of NF-κB1 mRNA. As shown in Figure2(b), the relative luciferase activities of the pre-miR-16 groups transfected with NF-κB1 3′-UTR constructs were significantly decreased, compared to those transfected with pMIR-NF-κB1 constructs, for the 293T cell line, implying that NF-κB1 is a direct target of miR-16. To further demonstrate the correlation between miR-16 and NF-κB1, mRNA and protein expression of NF-κB1 were detected by qRT-PCR and Western blotting. Data showed that miR-16 upregulation dramatically reduced the protein expression of NF-κB1. Meanwhile, we observed that NF-κB1 expression was increased by downregulating miR-16 (Fig.2c,d). Thus, miR-16 inhibited NF-κB1 expression in human glioma.
Affiliation: Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.