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The Effect of miR-200c Inhibition on Chemosensitivity (5- FluoroUracil) in Colorectal Cancer

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Pathology & Oncology Research

Abstract

5-Fluorouracil (5-FU) as a chemotherapeutic drug is used to treat colorectal cancer (CRC). However, 5-FU is associated with acquired CRC resistance, which decreases the therapeutic potential of 5-FU. Several studies indicated that miR-200c is also involved in chemotherapeutic drug resistance, but the exact mechanism of miR-200c mediated chemoresistance has not yet been fully understood. In this study, we examined the effect of inhibition of miR-200c on the sensitivity of HCT-116 cells to 5-FU. HCT-116 cells were transfected with LNA-anti- miR-200c for 48 h. mRNA expression of miR-200c was investigated by qRT-PCR. The protein expression of phosphatase and tensin homolog (PTEN) and E-cadherin were evaluated by western blotting. Annexin V/ PI staining and caspase 3 activity were used to detect apoptosis. LNA-anti-miR-200c inhibited the miR-200c expression in the transfected cells compared with that in the control group. LNA-anti-miR-200c suppressed the expression of PTEN and E-cadherin independent of the presence of the chemotherapeutic drug 5-FU. LNA-anti-miR-200c reduced the 5-FU-induced apoptosis and caspase 3 activity. miR-200c, as a novel prognostic marker in CRC, can be a potential therapeutic approach to overcome chemoresistance during 5-FU chemotherapy.

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Acknowledgements

This study was funded by the Hamadan University of Medical Sciences (grant no.: 9407073722).

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Authors and Affiliations

  1. Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Korosh Heydari, Massoud Saidijam, Fatemeh Karimi dermani, Nooshin Shabab & Rezvan Najafi

  2. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Mohammad reza Sharifi

  3. Department of Anatomy, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Sara Soleimani Asl

  4. Endometrium and Endometriosis Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

    Sara Soleimani Asl & Rezvan Najafi

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  1. Korosh Heydari
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Correspondence to Rezvan Najafi.

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Heydari, K., Saidijam, M., Sharifi, M.r. et al. The Effect of miR-200c Inhibition on Chemosensitivity (5- FluoroUracil) in Colorectal Cancer. Pathol. Oncol. Res. 24, 145–151 (2018). https://doi.org/10.1007/s12253-017-0222-6

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  • DOI: https://doi.org/10.1007/s12253-017-0222-6

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