title: MicroRNA-138 negatively regulates non-small cell lung cancer cells through the interaction with cyclin D3.
abstract: Previous studies demonstrate that microRNA-138 (miR-138) is critical in non-small cell lung cancer (NSCLC) regulation. We further explored the molecular mechanism of miR-138 in NSCLC. Lentivirus was used to upregulate miR-138 in NSCLC cell lines H460 and SPC-A1 cells. Previously known effects of miR-138 upregulation on NSCLC, proliferation, cell cycle division, and cisplatin sensitivity were examined in H460 and SPC-A1 cells. Moreover, previously unknown effect of miR-138 upregulation on NSCLC migration was also examined in H460 and SPC-A1 cells. A new miR-138 downstream target, cyclin D3 (CCND3), was assessed by dual-luciferase reporter assay and quantitative real-time PCR (qRT-PCR). CCND3 was then ectopically overexpressed in H460 and SPC-A1 cells. The effects of forced overexpression of CCND3 on miR-138-induced NSCLC regulations were further examined by proliferation, cell cycle, cisplatin sensitivity, and migration assays, respectively. Lentivirus-induced miR-138 upregulation inhibited NSCLC proliferation and cell cycle division, in line with previous findings. Moreover, we found that miR-138 upregulation had other anti-tumor effects, such as increasing cisplatin sensitivity and reducing cancer migration, in H460 and SPC-A1 cells. Luciferase assay and qRT-PCR showed that CCND3 was directly targeted by miR-138. Forced overexpression of CCND3 in H460 and SPC-A1 cells reversed the anti-tumor effects of miR-138 upregulation on cancer cell growth, cell cycle, cisplatin sensitivity, and migration. Our study revealed novel anti-cancer effects of miR-138 upregulation in NSCLC, as well as its new molecular target of CCND3.
authors.affiliation: Department of Respiratory Medicine, Jining First People's Hospital, 6 Jiankang Road, Jining, 272000, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Han
authors.affiliation: Department of Respiratory Medicine, Jining First People's Hospital, 6 Jiankang Road, Jining, 272000, China. tianfu2@aol.com.
authors.forename: Tian
authors.initials: T
authors.lastname: Fu
authors.affiliation: Department of Respiratory Medicine, Jining First People's Hospital, 6 Jiankang Road, Jining, 272000, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Respiratory Medicine, Jining First People's Hospital, 6 Jiankang Road, Jining, 272000, China.
authors.forename: Jian-Long
authors.initials: JL
authors.lastname: Miao
authors.affiliation: Department of Respiratory Medicine, Jining First People's Hospital, 6 Jiankang Road, Jining, 272000, China.
authors.forename: Qiu-Fang
authors.initials: QF
authors.lastname: Jiang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002945:Cisplatin / Q000737:chemistry; D056743:Cyclin D3 / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; C534696:CCND3 protein, human; D056743:Cyclin D3; C546110:MIRN138 microRNA, human; D035683:MicroRNAs; D002945:Cisplatin
keywords: CCND3; Cisplatin; NSCLC; miR-138