title: MicroRNA-520a-5p displays a therapeutic effect upon chronic myelogenous leukemia cells by targeting STAT3 and enhances the anticarcinogenic role of capsaicin.
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.
authors.affiliation: Medical Biology Department, Ege University School of Medicine, Izmir, Turkey, bt1980@gmail.com.
authors.forename: Burçin Tezcanlı
authors.initials: BT
authors.lastname: Kaymaz
authors.forename: Vildan Bozok
authors.initials: VB
authors.lastname: Cetintaş
authors.forename: Cağdaş
authors.initials: C
authors.lastname: Aktan
authors.forename: Buket
authors.initials: B
authors.lastname: Kosova
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D002211:Capsaicin / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors
chemical_list: D016588:Anticarcinogenic Agents; C575048:MIRN520 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D002211:Capsaicin