Research Papers:

MicroRNA-26b inhibits tumor metastasis by targeting the KPNA2/c-jun pathway in human gastric cancer

Ming-Ming Tsai, Hsiang-Wei Huang, Chia-Siu Wang, Kam-Fai Lee, Chung-Ying Tsai, Pei-Hsuan Lu, Hsiang-Cheng Chi, Yang-Hsiang Lin, Liang-Mou Kuo and Kwang-Huei Lin _

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Oncotarget. 2016; 7:39511-39526. https://doi.org/10.18632/oncotarget.8629

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Ming-Ming Tsai1,3,*, Hsiang-Wei Huang2,*, Chia-Siu Wang3,*, Kam-Fai Lee4, Chung-Ying Tsai2, Pei-Hsuan Lu5, Hsiang-Cheng Chi2, Yang-Hsiang Lin2, Liang-Mou Kuo3, Kwang-Huei Lin2,6

1Department of Nursing, Division of Basic Medical Sciences and Research Center for Industry of Human Ecology, Chang-Gung University of Science and Technology, Taoyuan, 333, Taiwan

2Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan, 333, Taiwan

3Department of General Surgery, Chang Gung Memorial Hospital at Chia-yi, Chia-yi, 613, Taiwan

4Department of Pathology, Chang Gung Memorial Hospital, Chia-yi, 613, Taiwan

5Department of Dermatology, Chang Gung Memorial Hospital, Chang Gung University, Taipei, 10508, Taiwan

6Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, 333, Taiwan

*These authors contributed equally to this work

Correspondence to:

Kwang-Huei Lin, email: [email protected]

Keywords: miR-26b, KPNA2, c-jun, prognosis, gastric cancer

Received: July 17, 2015     Accepted: March 12, 2016     Published: April 07, 2016


MicroRNAs (miRNA) play an important role in carcinogenesis. Previously, we identified miR-26b as a significantly downregulated miRNA in gastric cancer (GC) tissues (n = 106) based on differential quantitative RT-PCR (RT-qPCR) miRNA expression profiles. In the current study, we aimed to clarify the potential role of miR-26b and related target genes in GC progression. Downregulation of miR-26b was associated with advanced tumor-node-metastasis stage (TNM stage) and poor 5-year survival rate. Forced expression of miR-26b led to inhibition of GC cell migration and invasion in vitro and lung metastasis formation in vivo. Conversely, depletion of miR-26b had stimulatory effects. Additionally, miR-26b affected GC cell behavior through negative regulation of the metastasis promoter, karyopherin alpha 2 (KPNA2). Ectopic expression of miR-26b induced a reduction in KPNA2 protein levels, confirmed by luciferase assay data showing that miR-26b directly binds to the 3’ untranslated regions (UTR) of KPNA2 mRNA. Furthermore, miR-26b and KPNA2 mRNA/protein expression patterns were inversely correlated in GC tissues. Cag A of Helicobacter pylori (Hp) enhanced miR-26b levels through regulation of the KPNA2/c-jun pathway. Taken together, our data indicate that miR-26b plays an anti-metastatic role and is downregulated in GC tissues via the KPNA2/c-jun pathway. Based on the study findings, we propose that miR-26b overexpression or KPNA2/c-jun suppression may have therapeutic potential in inhibiting GC metastasis.

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