title: MicroRNA-192 targeting retinoblastoma 1 inhibits cell proliferation and induces cell apoptosis in lung cancer cells.
abstract: microRNAs play an important roles in cell growth, differentiation, proliferation and apoptosis. They can function either as tumor suppressors or oncogenes. We found that the overexpression of miR-192 inhibited cell proliferation in A549, H460 and 95D cells, and inhibited tumorigenesis in a nude mouse model. Both caspase-7 and the PARP protein were activated by the overexpression of miR-192, thus suggesting that miR-192 induces cell apoptosis through the caspase pathway. Further studies showed that retinoblastoma 1 (RB1) is a direct target of miR-192. Over-expression of miR-192 decreased RB1 mRNA and protein levels and repressed RB1-3'-UTR reporter activity. Knockdown of RB1 using siRNA resulted in a similar cell morphology as that observed for overexpression of miR-192. Additionally, RB1-siRNA treatment inhibited cell proliferation and induced cell apoptosis in lung cancer cells. Analysis of miRNA expression in clinical samples showed that miR-192 is significantly downregulated in lung cancer tissues compared to adjacent non-cancerous lung tissues. In conclusion, our results demonstrate that miR-192 is a tumor suppressor that can target the RB1 gene to inhibit cell proliferation and induce cell apoptosis in lung cancer cells. Furthermore, miR-192 was expressed at low levels in lung cancer samples, indicating that it might be a promising therapeutic target for lung cancer treatment.
authors.affiliation: Lab for RNA Chemical Biology at Guangzhou Institutes of Biomedicine and Health, Chinese Academic of Science, Guangzhou 510530, China.
authors.forename: Shipeng
authors.initials: S
authors.lastname: Feng
authors.forename: Shujie
authors.initials: S
authors.lastname: Cong
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Xichen
authors.initials: X
authors.lastname: Bao
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Huiping
authors.initials: H
authors.lastname: Li
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Guoxin
authors.initials: G
authors.lastname: Wang
authors.forename: Jianzhen
authors.initials: J
authors.lastname: Xu
authors.forename: Bowen
authors.initials: B
authors.lastname: Du
authors.forename: Dezhong
authors.initials: D
authors.lastname: Qu
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.forename: Menghui
authors.initials: M
authors.lastname: Yin
authors.forename: Xiaoshuai
authors.initials: X
authors.lastname: Ren
authors.forename: Feifei
authors.initials: F
authors.lastname: Wang
authors.forename: Jianxing
authors.initials: J
authors.lastname: He
authors.forename: Biliang
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D034622:RNA Interference; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: C546783:MIRN192 microRNA, human; D035683:MicroRNAs; D016160:Retinoblastoma Protein