title: MiR-183 promotes growth of non-small cell lung cancer cells through FoxO1 inhibition.
abstract: Non-small cell lung cancer (NSCLC) is a prevalent cancer in lung of high incidence. NSCLCs often appear to be fast growing, which renders comprehension of the mechanisms underlying the growth of NSCLC extremely critical. Previous study has addressed a role of microRNA (miR) family member, miR-183, in the regulation of the invasiveness of NSCLC, whereas the role of miR-183 in the growth control of NSCLC is not clear. Here, we analyzed the regulation of FoxO1 by miR-183 in vitro using luciferase-reporter assay. We also analyzed the effects of miR-183 on NSCLC cell growth in vitro using a microculture tetrazolium (MTT) assay and in vivo by visualizing tumor growth using bioluminescence assay. We found that overexpression of miR-183 in NSCLC cells decreased FoxO1 protein levels, whereas inhibition of miR-183 increased FoxO1 protein levels without affecting FoxO1 transcripts. Moreover, miR-183 bound to FoxO1 mRNA to prevent its translation through its 3'untranslated region (UTR). Furthermore, administration of miR-183 suppressed FoxO1 levels in NSCLC, resulting in a significant increase in NSCLC growth in vitro and in vivo, while administration of antisense of miR-183 significantly increased FoxO1 levels in NSCLC resulting in a significant decrease in NSCLC growth. Taken together, our data demonstrate that miR-183/FoxO1 axis may be a novel therapeutic target for regulating the growth of NSCLC.
authors.affiliation: Department of Respiratory Diseases, Beijing Military Region General Hospital of PLA, 5 Nanmencang, Dongcheng District, Beijing, 100700, China. liqun_zhang15@163.com.
authors.forename: Liqun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Battalion 19 of the Department of Biomedical Engineering, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Quan
authors.affiliation: Department of Respiratory Diseases, Beijing Military Region General Hospital of PLA, 5 Nanmencang, Dongcheng District, Beijing, 100700, China.
authors.forename: Sihai
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Respiratory Diseases, Beijing Military Region General Hospital of PLA, 5 Nanmencang, Dongcheng District, Beijing, 100700, China.
authors.forename: XueHui
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Respiratory Diseases, Beijing Military Region General Hospital of PLA, 5 Nanmencang, Dongcheng District, Beijing, 100700, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Che
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C533449:MIRN183 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: FoxO1; Non-small cell lung cancer (NSCLC); miR-183