title: Sp1-mediated microRNA-182 expression regulates lung cancer progression.
abstract: Our recent study indicated that overexpression of Sp1 enhances the proliferation of lung cancer cells, while represses metastasis. In this study, we found that the transcriptional activity of FOXO3 was increased, but its protein levels decreased following Sp1 expression. Sp1 increased expression of miR-182, which was then recruited to the 3'-untranslated region of FOXO3 mRNA to silence its translational activity. Knockdown of miR-182 inhibited lung cancer cells growth, but enhanced the invasive and migratory abilities of these cells through increased N-cadherin expression. Repression of FOXO3 expression in the miR-182 knockdown cells partially reversed this effect, suggesting that miR-182 promotes cancer cell growth and inhibits cancer metastatic activity by regulating the expression of FOXO3. The expression of several cancer metastasis-related genes such as ADAM9, CDH9 and CD44 was increased following miR-182 knockdown. In conclusion, in the early stages of lung cancer progression, Sp1 stimulates miR-182 expression, which in turn decreases FOXO3 expression. This stimulates proliferation and tumor growth. In the late stages, Sp1 and miR-182 decline, thus increasing FOXO3 expression, which leads to lung metastasis.
authors: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience in Biotechnology, National Cheng Kung University, Tainan 701, Taiwan.
authors: Wen-Bin
authors: WB
authors: Yang
authors: Ping-Hsin
authors: PH
authors: Chen
authors: Tsung
authors: T
authors: Hsu
authors: Tzu-Fun
authors: TF
authors: Fu
authors: Wu-Chou
authors: WC
authors: Su
authors: Hungjiun
authors: H
authors: Liaw
authors: Wen-Chang
authors: WC
authors: Chang
authors: Jan-Jong
authors: JJ
authors: Hung
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D018929:Cell Culture Techniques; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D035683:MicroRNAs; C538984:Mirn182 microRNA, human; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human