Oncotarget

Research Papers:

Sp1-mediated microRNA-182 expression regulates lung cancer progression

Wen-Bin Yang, Ping-Hsin Chen, Tsung-I Hsu, Tzu-Fun Fu, Wu-Chou Su, Hungjiun Liaw, Wen-Chang Chang and Jan-Jong Hung _

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Oncotarget. 2014; 5:740-753. https://doi.org/10.18632/oncotarget.1608

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Abstract

Wen-Bin Yang1, Ping-Hsin Chen2, Tsung-I Hsu3, Tzu-Fun Fu4, Wu-Chou Su5, Hungjiun Liaw6, Wen-Chang Chang7 and Jan-Jong Hung1,2,3,7,

1 Institute of Bioinformatics and Biosignal Transduction, College of Bioscience in Biotechnology, National Cheng Kung University, Tainan 701, Taiwan

2 Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan

3 Center for Infectious Disease and Signal Transduction Research, National Cheng Kung University, Tainan 701, Taiwan

4 Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan

5 Department of Internal Medicine, College of Medicine and Hospital, National Cheng Kung University, Tainan 701, Taiwan

6 Department of Life Sciences, College of Bioscience in Biotechnology, National Cheng Kung University, Tainan 701, Taiwan

7 Graduate Institute of Medical Sciences, College of Medicine, and Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei 110, Taiwan

Correspondence:

petehung, email:

Keywords: Sp1, miR-182, FOXO3, Lung cancer

Received: November 18, 2013 Accepted: January 24, 2014 Published: January 25, 2014

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.


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