Revealing genome-wide mRNA and microRNA expression patterns in leukemic cells highlighted 'hsa-miR-2278' as a tumor suppressor for regain of chemotherapeutic imatinib response due to targeting STAT5A

Autor: Burçin Tezcanlı Kaymaz, Sezgi Kipcak, Nur Selvi Günel, Çağdaş Aktan, Melis Kartal Yandim, Buket Kosova Can, Aysun Adan Gökbulut, Buket Özel, Yusuf Baran, Metin Ceyhan, Vildan Bozok Çetintaş
Přispěvatelé: AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü, Baran, Yusuf, TR119193, Kartal Yandım, Melis, Adan Gökbulut, Aysun, Izmir Institute of Technology. Molecular Biology and Genetics
Rok vydání: 2015
Předmět:
Small interfering RNA
medicine.drug_class
Blotting
Western
Apoptosis
Biology
Real-Time Polymerase Chain Reaction
Tyrosine-kinase inhibitor
hemic and lymphatic diseases
Leukemia
Myelogenous
Chronic
BCR-ABL Positive
microRNA
medicine
Biomarkers
Tumor
STAT5 Transcription Factor
Tumor Cells
Cultured
Humans
RNA
Messenger
Imatinib resistance
RNA
Small Interfering
Protein Kinase Inhibitors
Cell Proliferation
Oligonucleotide Array Sequence Analysis
Cell growth
Gene Expression Regulation
Leukemic
Genome
Human
Reverse Transcriptase Polymerase Chain Reaction
Gene Expression Profiling
Tumor Suppressor Proteins
Chronic myeloid leukemia
Myeloid leukemia
Transcriptome and miRNome array
Imatinib
General Medicine
Transfection
STAT5A
MicroRNAs
Drug Resistance
Neoplasm
siRNA
Cancer research
Imatinib Mesylate
medicine.drug
Zdroj: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 36(10)
ISSN: 1423-0380
Popis: BCR-ABL oncoprotein stimulates cell proliferation and inhibits apoptosis in chronic myeloid leukemia (CML). For cure, imatinib is a widely used tyrosine kinase inhibitor, but developing chemotherapeutic resistance has to be overcome. In this study, we aimed to determine differing genome-wide microRNA (miRNA) and messenger RNA (mRNA) expression profiles in imatinib resistant (K562/IMA-3 μM) and parental cells by targeting STAT5A via small interfering RNA (siRNA) applications. After determining possible therapeutic miRNAs, we aimed to check their effects upon cell viability and proliferation, apoptosis, and find a possible miRNA::mRNA interaction to discover the molecular basis of imatinib resistance. We detected that miR-2278 and miR-1245b-3p were most significantly regulated miRNAs according to miRNome array. Upregulating miR-2278 expression resulted in the inhibition of resistant leukemic cell proliferation and induced apoptosis, whereas miR-1245b-3p did not exhibit therapeutic results. Functional analyses indicated that AKT2, STAM2, and STAT5A mRNAs were functional targets for miR-2278 as mimic transfection decreased their expressions both at transcriptional and translational level, thus highlighting miR-2278 as a tumor suppressor. This study provides new insights in discovering the mechanism of imatinib resistance due to upregulating the tumor-suppressor hsa-miR-2278 which stands for a functional therapeutic approach, inhibited leukemic cell proliferation, induced apoptosis, and regain of chemotherapeutic drug response in CML therapy. © 2015, International Society of Oncology and BioMarkers (ISOBM).
Ege University Research Fund (APAK 2013-TIP/083)
Databáze: OpenAIRE
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