title: MicroRNA-141 and its associated gene FUS modulate proliferation, migration and cisplatin chemosensitivity in neuroblastoma cell lines.
abstract: In the present study, a novel signaling pathway of microRNA-141 (miR-141)/fused in sarcoma (FUS) was investigated in neuroblastoma (NB). Gene expression of miR-141 was evaluated in 6 NB cell lines. IMR-32 and SH-SY5Y cells were transduced with the miR-141 mimic lentivirus. The effects of miR-141 upregulation on cell proliferation, cell division, migration, chemosensitivity and in vivo explants were evaluated by MTT, cell cycle, wound-healing, cisplatin sensitivity and in vivo tumor growth assays, respectively. The correlation between miR-141 and the FUS gene was evaluated by luciferase assay and qRT-PCR. FUS was also downregulated in IMR-32 and SH-SY5Y cells to evaluate its impact on NB regulation. miR-141 was downregulated in both MYCN‑ and non-MYCN‑amplified NB cell lines. In the IMR-32 and SH-SY5Y cells, lentivirus-induced miR-141 upregulation inhibited cancer proliferation, cell cycle progression, migration and increased cisplatin chemosensitivity in vitro. In addition, miR-141 upregulation reduced the in vivo growth of IMR-32 tumor explants. FUS was found to be inversely regulated by miR-141 in NB. Small interfering RNA (siRNA)-induced FUS downregulation had similar tumor-suppressive effects as miR-141 upregulation on NB cell proliferation, cell cycle progression, migration and cisplatin chemosensitivity. Our data indicate that miR-141 and the FUS gene, which are inversely correlated, play significant functional roles in regulating human NB.
authors.affiliation: Emergency Department, Linyi People's Hospital, Linyi, Shandong 276001, P.R. China.
authors.forename: Ziran
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Emergency Department, Linyi People's Hospital, Linyi, Shandong 276001, P.R. China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Lei
authors.affiliation: Department of Medical Imaging, Linyi People's Hospital, Linyi, Shandong 276001, P.R. China.
authors.forename: Quanyu
authors.initials: Q
authors.lastname: Sun
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D006801:Humans; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034702:RNA-Binding Protein FUS / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; C000599550:FUS protein, human; C533895:MIRN141 microRNA, human; D035683:MicroRNAs; D034702:RNA-Binding Protein FUS; D002945:Cisplatin