MicroRNA-103 confers the resistance to long-treatment of adriamycin to human leukemia cells by regulation of COP1.

Abstract

Adriamycin (ADR) is an anti-cancer drug which offers improvement in survival for acute myeloid leukemia (AML) patients. However, the drug resistance is almost inevitable. Increasing evidences suggested that microRNAs (miRNAs) were associated with cancer chemo-resistance. Here, we aimed to explore the possible mechanism of miR-103 affected resistance to ADR in AML cells. Different concentrations of ADR were used to induce K562 and KASUMI-1 cells, and miR-103 mimic, inhibitor were transfected into K562 and KASUMI-1 cells. Cell viability and proliferation were determined by trypan blue staining and MTT assays for evaluating K562 and KASUMI-1 cells drug resistance. The relationship of miR-103 and COP1, Trib1, and C/EBPα were analyzed by qRT-PCR and Western blot. Cell proliferation, viability were detected again. Besides, the expressions of main factors of cell cycle and PI3K/AKT signal pathway were analyzed by Western blot. Results showed that ADR inhibited cell viability and proliferation in K562 and KASUMI-1 cells. However, K562 and KASUMI-1 cells appeared drug resistance for 50 passages at 0.8 µM of ADR. In addition, miR-103 expression was up-regulated in ADR-resistant K562 cells (K562/ADR) and overexpression of miR-103 increased K562 cells drug resistance via promoting cell viability and cell cycle-related factors expressions. COP1 was positively regulated by miR-103, suppression of miR-103 recovered K562/ADR cells drug resistance by regulation of COP1, Trib1, and C/EBPα. Besides, miR-103 blocked PI3K/AKT signal pathway by regulation of COP1. These data indicated that miR-103 was up-regulated in drug resistant cells and it may regulate ADR-resistance by regulation of COP1 in AML cells.

• Authors: Lin Wan, Yanlong Tian, Rui Zhang, Zhuo Peng, Jiangli Sun, Wanggang Zhang
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 119 Issue 5 Pg. 3843-3852 (05 2018) ISSN: 1097-4644 [Electronic] United States
• PMID: 29058777 (Publication Type: Journal Article, Retracted Publication)
• Copyright: © 2017 Wiley Periodicals, Inc.

Chemical References

• MIRN103 microRNA, human
• MicroRNAs
• Neoplasm Proteins
• RNA, Neoplasm
• Doxorubicin
• COP1 protein, human
• Ubiquitin-Protein Ligases

Topics

• Doxorubicin (pharmacology)
• Drug Resistance, Neoplasm (drug effects)
• Gene Expression Regulation, Enzymologic (drug effects)
• Gene Expression Regulation, Leukemic (drug effects)
• Humans
• K562 Cells
• Leukemia, Myeloid, Acute (drug therapy, genetics, metabolism, pathology)
• MicroRNAs (genetics, metabolism)
• Neoplasm Proteins (biosynthesis, genetics)
• RNA, Neoplasm (genetics, metabolism)
• Ubiquitin-Protein Ligases (biosynthesis, genetics)