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MicroRNA-520a-5p displays a therapeutic effect upon chronic myelogenous leukemia cells by targeting STAT3 and enhances the anticarcinogenic role of capsaicin

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Tumor Biology

Abstract

Aberrant expression profiles of microRNAs (miRNAs) have been previously demonstrated for having essential roles in a wide range of cancer types including leukemia. Antiproliferative or proapoptotic effects of capsaicin have been reported in several cancers. We aimed to study miRNAs involved in the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway in chronic myeloid leukemia cell model and the effects of the capsaicin treatment on cell proliferation and miRNA regulation. miR-520a-5p expression was extremely downregulated in capsaicin-treated cells. Repressing the level of miR-520a-5p by transient transfection with specific miRNA inhibitor oligonucleotides resulted in induced inhibition of proliferation in leukemic cells. According to bioinformatics analysis, STAT3 messenger RNA was predicted as a putative miR-520a-5p target; which was confirmed by quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR) and Western blot analysis. Cell proliferation inhibition was enhanced upon knockdown of STAT3 by RNA interference applications, but when miR-520a-5p inhibitor was additionally transfected onto STAT3 silenced cells, cell viability was dramatically decreased in leukemia cells. Finally, we observed the effects of capsaicin following miR-520a-5p inhibitor transfection upon cell proliferation, apoptosis, and STAT3 expression levels. We determined that, downregulation of miR-520a-5p affected the proliferation inhibition enhanced by capsaicin and reduced STAT3 mRNA and protein expression levels and increased apoptotic cell number. In summary, miR-520a-5p displays a therapeutic effect by targeting STAT3 and impacting the anticancer effects of capsaicin; whereas capsaicin, potentially through the miR-520a-5p/STAT3 interaction, induces apoptosis and inhibits K562 leukemic cell proliferation with need of further investigation.

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Acknowledgment

We gratefully thank Prof. Dr. Cumhur Gündüz from Ege University Medical School, Medical Biology Department, for his assistance in apoptosis assay by directing us in flow cytometer analyses results.

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Authors and Affiliations

  1. Medical Biology Department, Ege University School of Medicine, Izmir, Turkey

    Burçin Tezcanlı Kaymaz, Vildan Bozok Çetintaş, Çağdaş Aktan & Buket Kosova

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  1. Burçin Tezcanlı Kaymaz
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  2. Vildan Bozok Çetintaş
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Correspondence to Burçin Tezcanlı Kaymaz.

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Kaymaz, B.T., Çetintaş, V.B., Aktan, Ç. et al. MicroRNA-520a-5p displays a therapeutic effect upon chronic myelogenous leukemia cells by targeting STAT3 and enhances the anticarcinogenic role of capsaicin. Tumor Biol. 35, 8733–8742 (2014). https://doi.org/10.1007/s13277-014-2138-z

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  • DOI: https://doi.org/10.1007/s13277-014-2138-z

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