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miR494 inhibits cancerinitiating cell phenotypes and reverses resistance to lapatinib by downregulating FGFR2 in HER2positive gastric cancer

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In gastric cancer, >15% of cases are associated with the amplification of human epidermal growth factor receptor 2 (HER2), which leads to poor clinical outcomes. Lapatinib, a potent ATPcompetitive inhibitor, is a small, orally active molecule, which inhibits the tyrosine kinases of HER2 and epidermal growth factor receptor type 1. The activation of receptor tyrosine kinases can contribute to lapatinib resistance in HER2positive gastric cancer. The aim of the present study was to explore the effects of miR494 and FGFR2 in regulation of cancerinitiating cell phenotypes and therapeutic efficiency of lapatinib in HER2positive gastric cancer. Western blot analysis was used to identify that the expression of fibroblast growth factor receptor 2 (FGFR2), a receptor tyrosine kinase, was upregulated in gastric cancer tissues. Formation of cancer initiating cells (CICs) and resistance to lapatinib were determined using sphere growth assay and MTT assay, respectively. The overexpression of FGFR2 promoted the generation of cancerinitiating cells (CICs) and resistance to lapatinib in HER2positive gastric cancer YCC1 cells. In addition, it was observed that overexpression of microRNA (miR)494 downregulated the protein expression of FGFR2, inhibited the formation of CICs and reversed lapatinib resistance in YCC1F cells (HER2positive, FGFR2 overexpressing and lapatinibresistant gastric cancer cells). Therefore, it was concluded that miR494 inhibited the CIC phenotype and reversed resistance to lapatinib by inhibiting FGFR2 in HER2positive gastric cancer.
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Document Type: Research Article

Affiliations: 1: Cancer Treatment Research Center, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China 2: Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China

Publication date: January 1, 2018

More about this publication?
  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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