microRNA‑125b promotes leukemia cell resistance to daunorubicin by inhibiting apoptosis.

Abstract

microRNA-125b (miR-125b) is overexpressed in several types of cancer and contributes to tumor resistance to chemotherapy. The present study investigated the effect of miR-125b on the resistance of leukemia cell lines to the chemotherapeutic agent daunorubicin (DNR). miR-125b expression was found to be upregulated in patients who had failed therapy compared with those who demonstrated event-free survival. The overexpression of miR-125b was observed to induce DNR resistance in K562, THP‑1 and Jurkat cells by reducing apoptosis, whereas the suppression of miR-125b was found to enhance DNR cytotoxicity in REH cells. Furthermore, miR-125b was observed to mediate DNR resistance in leukemia cell lines through decreasing expression of G protein-coupled receptor kinase 2 and p53-upregulated modulator of apoptosis, which were shown to be direct targets of miR-125b using a dual-luciferase reporter. The present study provides a novel mechanism for understanding leukemia drug resistance and provides a novel method for calculating patient prognosis.

• Authors: Lili Zhou, Haitao Bai, Chun Wang, Daolin Wei, Youwen Qin, Xiaowei Xu
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 9 Issue 5 Pg. 1909-16 (May 2014) ISSN: 1791-3004 [Electronic] Greece
• PMID: 24604579 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• BBC3 protein, human
• MIRN125 microRNA, human
• MicroRNAs
• Proto-Oncogene Proteins
• G-Protein-Coupled Receptor Kinase 2
• Daunorubicin

Topics

• Adolescent
• Adult
• Aged
• Apoptosis (drug effects, genetics)
• Apoptosis Regulatory Proteins (genetics)
• Cell Line, Tumor
• Daunorubicin (pharmacology)
• Drug Resistance, Neoplasm (genetics)
• Female
• G-Protein-Coupled Receptor Kinase 2 (genetics)
• Gene Expression
• Gene Expression Regulation, Leukemic
• Gene Knockdown Techniques
• Humans
• Leukemia (diagnosis, genetics)
• Male
• MicroRNAs (genetics)
• Middle Aged
• Proto-Oncogene Proteins (genetics)
• Young Adult