title: MiR-181c modulates the proliferation, migration, and invasion of neuroblastoma cells by targeting Smad7.
abstract: MicroRNAs (miRNAs) function as key regulators of gene expression in various cancers. In this study, the aim is to explore the roles and regulation mechanism of miR-181c in neuroblastoma (NB) cells. We found that miR-181c was downregulated in metastatic NB tissues, compared with primary NB tissues. Then functional studies indicated that miR-181c overexpression inhibited NB cell proliferation, migration, and invasion, while miR-181c inhibition increased cell proliferation, migration, and invasion. EGFP reporter assay, real-time polymerase chain reaction and western blot analysis validated that Smad7 was a direct target of miR-181c. MiR-181c reduced Smad7 expression at both mRNA and protein levels. Finally, functional assays showed that the effect of Smad7 knockdown on cells was similar to that of miR-181c overexpression. Importantly, Smad7 overexpression could restore the antitumor effects that were induced by miR-181c. In conclusion, our results demonstrated that miR-181c inhibits NB cell growth and metastasis-related traits through the suppression of Smad7, functioning as a tumor suppressor. Moreover, our results suggested that miR-181c may serve as an important therapeutic target for NB patients.
authors.affiliation: The Fourth Clinical Hospital of Minimally Invasive Neurosurgery, Harbin Medical University, Harbin 150001, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Li
authors.forename: Wu
authors.initials: W
authors.lastname: Yue
mesh_terms: D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009362:Neoplasm Metastasis; D009447:Neuroblastoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D051906:Smad7 Protein / Q000235:genetics* / Q000502:physiology*
chemical_list: C540193:MIrn181 microRNA, human; D035683:MicroRNAs; C497806:SMAD7 protein, human; D051906:Smad7 Protein
keywords: miR-181c; miRNA; neuroblastoma; smad7