Abstract
Objectives: Melatonin (MT) is a pineal hormone with antineoplastic potential. This study aims to explore the therapeutic potential and mechanism of MT on glioblastoma (GBM).
Methods: A human GBM cell line, LN229, was used to evaluate the function of MT. Cell viability, apoptosis, and migration were detected by CCK-8, flow cytometry, and transwell assays, respectively. The mRNA and protein expressions of specific genes were measured by qRT-PCR and western blot, respectively. The regulatory relationship between miR-16-5p and PIM1 was validated by dual luciferase reporter gene assay. A mouse xenograft model was established to prove the anti-tumor effect and related mechanisms of MT in vivo.
Results: MT inhibited the viability and migration and promoted the apoptosis of LN229 cells in a dose-dependent manner. MiR-16-5p was dose-dependently up-regulated by MT in LN229 cells, negatively regulating its target PIM1. MiR-16-5p inhibitor eliminated the anti-tumor effect of MT in LN229 cells, while si-PIM1 reversed the effect of miR-16-5p inhibitor in MT-treated cells. MT inhibited the tumor growth in vivo and MT-induced PIM1 down-regulation was reversed by miR- 16-5p inhibition in tumor tissues.
Conclusions: MT inhibits the malignant progression of GBM via regulating miR-16-5p-mediated PIM1.
Keywords: Glioblastoma, melatonin, microRNA-16-5p, PIM1, malignant progression, in vivo experiments.
[http://dx.doi.org/10.1016/j.ctrv.2019.101896] [PMID: 31541850]
[http://dx.doi.org/10.1007/s12253-014-9833-3] [PMID: 25156108]
[http://dx.doi.org/10.2174/0929867324666170516123206] [PMID: 28521700]
[http://dx.doi.org/10.1038/nrneurol.2015.242] [PMID: 26782337]
[http://dx.doi.org/10.1007/s11912-017-0644-z] [PMID: 29075865]
[http://dx.doi.org/10.1007/s12094-016-1497-x] [PMID: 26960561]
[http://dx.doi.org/10.1097/MD.0000000000014099] [PMID: 30653130]
[http://dx.doi.org/10.1016/j.neuchi.2015.03.002] [PMID: 25908646]
[http://dx.doi.org/10.2174/1570159X14666161228122115] [PMID: 28503116]
[http://dx.doi.org/10.3390/molecules23030518] [PMID: 29495398]
[http://dx.doi.org/10.3390/cells9030599] [PMID: 32138190]
[http://dx.doi.org/10.1111/jpi.12052] [PMID: 23551342]
[http://dx.doi.org/10.7150/ijbs.16818] [PMID: 28255276]
[http://dx.doi.org/10.1016/j.tice.2021.101617] [PMID: 34418770]
[http://dx.doi.org/10.12659/MSM.917867] [PMID: 31860636]
[http://dx.doi.org/10.1016/0092-8674(84)90309-X] [PMID: 6327049]
[http://dx.doi.org/10.1038/nm.4198] [PMID: 27775704]
[http://dx.doi.org/10.1016/j.abb.2020.108413] [PMID: 32473133]
[http://dx.doi.org/10.1159/000492009] [PMID: 30045021]
[http://dx.doi.org/10.1016/j.biopha.2017.05.110] [PMID: 28570979]
[http://dx.doi.org/10.3390/nu11061343] [PMID: 31207928]
[http://dx.doi.org/10.1093/neuonc/nou216] [PMID: 25155357]
[http://dx.doi.org/10.3892/mmr.2021.11826] [PMID: 33398374]
[http://dx.doi.org/10.1111/jpi.12765] [PMID: 34487576]
[http://dx.doi.org/10.3892/or.2018.6282] [PMID: 29484412]
[http://dx.doi.org/10.2147/JIR.S305450] [PMID: 34079331]
[http://dx.doi.org/10.18632/aging.203561] [PMID: 34580235]
[http://dx.doi.org/10.3390/ijms22189907] [PMID: 34576070]
[http://dx.doi.org/10.1146/annurev.pathol.4.110807.092222] [PMID: 18817506]
[http://dx.doi.org/10.1016/j.yexmp.2020.104550] [PMID: 33010295]
[http://dx.doi.org/10.1089/dna.2017.4040] [PMID: 29359963]
[http://dx.doi.org/10.1042/BSR20191611] [PMID: 31383783]
[http://dx.doi.org/10.3389/fphar.2020.01324] [PMID: 32982740]
[PMID: 30657555]
[http://dx.doi.org/10.1038/s41598-019-48133-0] [PMID: 31406207]
[http://dx.doi.org/10.3892/or.2020.7682] [PMID: 32705237]
[http://dx.doi.org/10.7150/thno.10305] [PMID: 25897338]
[http://dx.doi.org/10.1016/j.lfs.2020.118934] [PMID: 33385405]
[http://dx.doi.org/10.1038/srep35350] [PMID: 27734929]
[http://dx.doi.org/10.3233/CBM-160038] [PMID: 27983525]
[http://dx.doi.org/10.2147/CMAR.S184381] [PMID: 30464610]