title: MicroRNA-26b inhibits tumor metastasis by targeting the KPNA2/c-jun pathway in human gastric cancer.
abstract: 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.
authors.affiliation: Department 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.|Department of General Surgery, Chang Gung Memorial Hospital at Chia-yi, Chia-yi, 613, Taiwan.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Tsai
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan, 333, Taiwan.
authors.forename: Hsiang-Wei
authors.initials: HW
authors.lastname: Huang
authors.affiliation: Department of General Surgery, Chang Gung Memorial Hospital at Chia-yi, Chia-yi, 613, Taiwan.
authors.forename: Chia-Siu
authors.initials: CS
authors.lastname: Wang
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Chia-yi, 613, Taiwan.
authors.forename: Kam-Fai
authors.initials: KF
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan, 333, Taiwan.
authors.forename: Chung-Ying
authors.initials: CY
authors.lastname: Tsai
authors.affiliation: Department of Dermatology, Chang Gung Memorial Hospital, Chang Gung University, Taipei, 10508, Taiwan.
authors.forename: Pei-Hsuan
authors.initials: PH
authors.lastname: Lu
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan, 333, Taiwan.
authors.forename: Hsiang-Cheng
authors.initials: HC
authors.lastname: Chi
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan, 333, Taiwan.
authors.forename: Yang-Hsiang
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Department of General Surgery, Chang Gung Memorial Hospital at Chia-yi, Chia-yi, 613, Taiwan.
authors.forename: Liang-Mou
authors.initials: LM
authors.lastname: Kuo
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan, 333, Taiwan.|Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, 333, Taiwan.
authors.forename: Kwang-Huei
authors.initials: KH
authors.lastname: Lin
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000517:prevention & control; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000382:microbiology; D016896:Treatment Outcome; D028901:alpha Karyopherins / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D035683:MicroRNAs; D016755:Proto-Oncogene Proteins c-jun; D028901:alpha Karyopherins; C490630:KPNA2 protein, human; C528163:MIRN26 microRNA, human; C080866:cagA protein, Helicobacter pylori
keywords: KPNA2; c-jun; gastric cancer; miR-26b; prognosis