Inhibition of BCR/ABL Protein Expression by miR-203 Sensitizes for Imatinib Mesylate

Abstract

Selective inhibition of BCR/ABL expression by RNA interference has been demonstrated as an effective strategy in CML treatment and a reversal to imatinib resistance. microRNAs (miRNAs) are small regulatory RNAs involved in post-transcriptional gene regulation. miR-203 is supposed to directly regulate ABL and BCR/ABL expression, however, the role of miR-203 in imatinib-resistant cells is not clear. Here, we report that overexpression of miR-203 in BaF3-BCR/ABL cells with T315I mutant inhibited cell growth and colony formation ability. Furthermore, miR-203 increased sensitivity to imatinib in BaF3-BCR/ABLT315I cells, thereby antagonizing the main mechanism of resistance to imatinib.

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

“…Overexpression of miR-203 inhibited cell growth and colony formation ability of leukemic cells, whereas targeting BCR-ABL expression by siRNA in correlation with miR-203 mimic transfection restored the sensitivity to imatinib in cells expressing the imatinib resistant BCR-ABL kinase domain mutant T315I [21]. Similar to our aim, these two reported studies also put forward the molecular basis of imatinib resistance in the means of miRNA profiling approach combined with siRNA applications.…”

The Implication of Cancer Progenitor Cells and the Role of Epigenetics in the Development of Novel Therapeutic Strategies for Chronic Myeloid Leukemia

“…Furthermore, imatinib treatment was shown to induce the demethylation of the miR-203 promoter region, resulting in low expression of targeted BCR-ABL1 gene, and loss of proliferation in K562 and KU812 leukemic cells (317). In confirmation of the previous literature, miR-203 was significantly reduced in the bone marrow of CML patients compared to healthy subjects (205). Overexpression of miR-203 in the imatinib-resistant cell line, BaF3-BCR/ABL T315I significantly suppressed cell growth, limited colony formation, and increased percentage of cells in G1 phase.…”

A Bmi1-miRNAs Cross-Talk Modulates Chemotherapy Response to 5-Fluorouracil in Breast Cancer Cells

“…Resent findings also strongly suggest loss of miR-200c expression contribute to drug resistance [38]. Emerging evidences suggest the implication of miR-203 expression loss in cancers, such as cancer cell proliferation, invasion and drug resistance [39,40,41], but the exact mechanism is still unclear. Here, our results showed miR-203 targeted Bmi1 to elicit its role in breast cancer drug resistance.…”