Home LiteratureArticle Details
PMID: 25400827 Published · epublish English Journal Article

MiR-19a promotes epithelial-mesenchymal transition through PI3K/AKT pathway in gastric cancer.

International journal of clinical and experimental pathology ·Vol. 7 ·No. 10 ·2014-00-00 ·Pages 7286-96

Lu W, Xu Z, Zhang M, Zuo Y

Abstract

It has been reported that miR-19a was up-regulated in gastric cancer (GC), playing an oncogenic role. However, the underlying mechanism is still unknown. Therefore, in our present study, we investigated the role of miR-19a in gastric tissues as well as 2 GC cell lines. In vivo in clinical tissue level, we have detected basal expression level of miR-19a using real-time reversal transcriptional PCR (RT-PCR); in addition, the relevance between expression of miR-19a and clinic-pathological information was also analyzed. In vitro in cell line level, miR-19a was ectopically expressed using over expression and knock-down strategy. It was found that the overexpression of miR-19a was significantly associated with metastasis of GC and inferior overall prognosis on clinical tissue level; that promotes the proliferation, migration and invasion; and that overexpression of miR-19a can promote the epithelial-mesenchymal transition through activating PI3K/AKT pathway. Blocking the PI3K/AKT pathway could cancel the effect of miR-19a. All together, our results suggest that miR-19a could be used as a promising therapeutic target in the treatment of GC.

Keywords
EMT Gastric cancer PI3K-AKT miR-19a
MeSH Terms
Cell Line, Tumor Cell Movement Cell Proliferation Enzyme Activation Epithelial-Mesenchymal Transition/drug effects Female Humans Male MicroRNAs/genetics,metabolism Middle Aged Neoplasm Invasiveness Neoplasm Staging Phenotype Phosphatidylinositol 3-Kinase/metabolism Phosphoinositide-3 Kinase Inhibitors Protein Kinase Inhibitors/pharmacology Proto-Oncogene Proteins c-akt/antagonists & inhibitors,genetics,metabolism RNA Interference Signal Transduction Stomach Neoplasms/enzymology,genetics,pathology Time Factors Transfection
Chemicals
MIRN19 microRNA, human MicroRNAs Phosphoinositide-3 Kinase Inhibitors Protein Kinase Inhibitors Phosphatidylinositol 3-Kinase Proto-Oncogene Proteins c-akt
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lu Weidong
Department of Oncology, Zhangjiagang First People's Hospital, Suzhou University Zhangjiagang 215600, China.
Xu Zhen
Department of Oncology, Zhangjiagang First People's Hospital, Suzhou University Zhangjiagang 215600, China.
Zhang Min
Department of Oncology, Zhangjiagang First People's Hospital, Suzhou University Zhangjiagang 215600, China.
Zuo Yun
Department of Oncology, Zhangjiagang First People's Hospital, Suzhou University Zhangjiagang 215600, China.
References (31)
31 references, click to expand
  1. The miRNA-17∼92 cluster mediates chemoresistance and enhances tumor growth in mantle cell lymphoma via PI3K/AKT pathway activation.
    Leukemia. 2012 May;26(5):1064-72 PMID: 22116552
  2. Dynamic epigenetic regulation of the microRNA-200 family mediates epithelial and mesenchymal transitions in human tumorigenesis.
    Oncogene. 2012 Apr 19;31(16):2062-74 PMID: 21874049
  3. TP53 genomic status regulates sensitivity of gastric cancer cells to the histone methylation inhibitor 3-deazaneplanocin A (DZNep).
    Clin Cancer Res. 2012 Aug 1;18(15):4201-12 PMID: 22675170
  4. MicroRNAs as promising biomarkers for gastric cancer.
    Cancer Biomark. 2012;11(6):259-67 PMID: 23248184
  5. MicroRNA dysregulation in gastric cancer.
    Curr Pharm Des. 2013;19(7):1273-84 PMID: 23092346
  6. miR-19a promotes cell growth and tumorigenesis through targeting SOCS1 in gastric cancer.
    Asian Pac J Cancer Prev. 2013;14(2):835-40 PMID: 23621248
  7. MicroRNA-19a/b regulates multidrug resistance in human gastric cancer cells by targeting PTEN.
    Biochem Biophys Res Commun. 2013 May 10;434(3):688-94 PMID: 23603256
  8. Luteolin attenuates TGF-β1-induced epithelial-mesenchymal transition of lung cancer cells by interfering in the PI3K/Akt-NF-κB-Snail pathway.
    Life Sci. 2013 Dec 5;93(24):924-33 PMID: 24140887
  9. Silencing of the miR-17~92 cluster family inhibits medulloblastoma progression.
    Cancer Res. 2013 Dec 1;73(23):7068-78 PMID: 24145352
  10. miR-141 suppresses proliferation and motility of gastric cancer cells by targeting HDGF.
    Mol Cell Biochem. 2014 Mar;388(1-2):211-8 PMID: 24276755
  11. MicroRNA-362 induces cell proliferation and apoptosis resistance in gastric cancer by activation of NF-κB signaling.
    J Transl Med. 2014;12:33 PMID: 24495516
  12. miR-34a regulates cisplatin-induce gastric cancer cell death by modulating PI3K/AKT/survivin pathway.
    Tumour Biol. 2014 Feb;35(2):1287-95 PMID: 24068565
  13. The expression and clinical significance of miR-132 in gastric cancer patients.
    Diagn Pathol. 2014;9:57 PMID: 24621117
  14. MiR-19a/b modulate the metastasis of gastric cancer cells by targeting the tumour suppressor MXD1.
    Cell Death Dis. 2014;5:e1144 PMID: 24675462
  15. A microRNA polycistron as a potential human oncogene.
    Nature. 2005 Jun 9;435(7043):828-33 PMID: 15944707
  16. A microRNA expression signature of human solid tumors defines cancer gene targets.
    Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2257-61 PMID: 16461460
  17. Complex networks orchestrate epithelial-mesenchymal transitions.
    Nat Rev Mol Cell Biol. 2006 Feb;7(2):131-42 PMID: 16493418
  18. MicroRNA signatures in human cancers.
    Nat Rev Cancer. 2006 Nov;6(11):857-66 PMID: 17060945
  19. The inhibition of tumor cell intravasation and subsequent metastasis via regulation of in vivo tumor cell motility by the tetraspanin CD151.
    Cancer Cell. 2008 Mar;13(3):221-34 PMID: 18328426
  20. miRiad roles for the miR-17-92 cluster in development and disease.
    Cell. 2008 Apr 18;133(2):217-22 PMID: 18423194
  21. PI3 kinase/Akt signaling mediates epithelial-mesenchymal transition in hypoxic hepatocellular carcinoma cells.
    Biochem Biophys Res Commun. 2009 May 8;382(3):631-6 PMID: 19303863
  22. Epithelial-mesenchymal transitions in development and disease.
    Cell. 2009 Nov 25;139(5):871-90 PMID: 19945376
  23. miR-19 is a key oncogenic component of mir-17-92.
    Genes Dev. 2009 Dec 15;23(24):2839-49 PMID: 20008935
  24. Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis.
    Lancet Oncol. 2010 Feb;11(2):136-46 PMID: 20022810
  25. Epithelial-to-mesenchymal transition of murine liver tumor cells promotes invasion.
    Hepatology. 2010 Sep;52(3):945-53 PMID: 20564331
  26. mTORC1 and mTORC2 regulate EMT, motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways.
    Cancer Res. 2011 May 1;71(9):3246-56 PMID: 21430067
  27. Sonic hedgehog pathway promotes metastasis and lymphangiogenesis via activation of Akt, EMT, and MMP-9 pathway in gastric cancer.
    Cancer Res. 2011 Nov 15;71(22):7061-70 PMID: 21975935
  28. miR-30 inhibits TGF-β1-induced epithelial-to-mesenchymal transition in hepatocyte by targeting Snail1.
    Biochem Biophys Res Commun. 2012 Jan 20;417(3):1100-5 PMID: 22227196
  29. The miR-200 family regulates TGF-β1-induced renal tubular epithelial to mesenchymal transition through Smad pathway by targeting ZEB1 and ZEB2 expression.
    Am J Physiol Renal Physiol. 2012 Feb 1;302(3):F369-79 PMID: 22012804
  30. Clinical outcome prediction by microRNAs in human cancer: a systematic review.
    J Natl Cancer Inst. 2012 Apr 4;104(7):528-40 PMID: 22395642
  31. Losses of chromosome 5q and 14q are associated with favorable clinical outcome of patients with gastric cancer.
    Oncologist. 2012;17(5):653-62 PMID: 22531355
Article Info
Journal
International journal of clinical and experimental pathology
Abbr.
Int J Clin Exp Pathol
ISSN
1936-2625
Published
2014-00-00
Epub
2014-00-15
Pages
7286-96
Language
English
Region
United States
NLM ID
101480565
PMCID
PMC4230128
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com