論文 - 詳細
| RRC ID | 55966 |
|---|---|
| 著者 | Pan B, Yang J, Wang X, Xu K, Ikezoe T. |
| タイトル | miR-217 sensitizes chronic myelogenous leukemia cells to tyrosine kinase inhibitors by targeting pro-oncogenic anterior gradient 2. |
| ジャーナル | Exp Hematol |
| Abstract |
BCR-ABL1-independent mechanisms had been thought to mediate drug resistance to tyrosine kinase inhibitors (TKIs) in patients with chronic myelogenous leukemia (CML). The pro-oncogenic anterior gradient 2 (AGR2) mediates drug resistance of cancer cells. In this study, we observed an increased level of AGR2 in TKI-resistant CML cells. Silence of AGR2 in dasatinib-resistant K562 (K562DR) cells led to restored sensitivity to dasatinib both in vitro and in vivo. Exposure to dasatinib induced upregulation of AGR2 in K562 cells, which indicated a probable treatment-related drug resistance. We further investigated the potential interaction between microRNA (miRNA) and AGR2 in K562DR cells and found that downregulation of miR-217 was associated with overexpression of AGR2 in K562DR cells. Luciferase reporter assay identified that miR-217 negatively regulated expression of AGR2 through binding the 3'-untranslated region of AGR2. Hypermethylation of the CpG island on the promoter region of the MIR217 gene is a probable reason for the downregulation of miR-217 in dasatinib-treated K562 cells. Forced expression of miR-217 led to decreased expression of AGR2 as well as compromised TKI-resistant potential of K562DR cells. Similarly, overexpression of miR-217 resensitized K562DR cells to dasatinib treatment in a murine xenograft transplantation model. TKI treatment-induced drug resistance is correlated with a decrease of miR-217 and upregulation of AGR2. The miR-217/AGR2 interaction might be a potential therapeutic target in treating CML patients with TKI resistance. |
| 巻・号 | 68 |
| ページ | 80-88.e2 |
| 公開日 | 2018-12-1 |
| DOI | 10.1016/j.exphem.2018.09.001 |
| PII | S0301-472X(18)30798-7 |
| PMID | 30195077 |
| MeSH | 3' Untranslated Regions Animals Antineoplastic Agents / pharmacology* Cell Line, Tumor DNA Methylation Dasatinib / pharmacology Drug Resistance, Neoplasm / genetics Gene Expression Regulation, Leukemic* / drug effects Gene Expression Regulation, Leukemic* / genetics Humans Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology* Mice Mice, Inbred NOD MicroRNAs / biosynthesis MicroRNAs / genetics MicroRNAs / physiology* Mucoproteins Neoplasm Proteins / genetics* Neoplasm Proteins / metabolism Oncogene Proteins Promoter Regions, Genetic Protein Kinase Inhibitors / pharmacology* Protein-Tyrosine Kinases / antagonists & inhibitors Proteins / genetics* Proteins / metabolism RNA / metabolism RNA Interference RNA, Neoplasm / genetics RNA, Neoplasm / physiology* RNA, Small Interfering / genetics RNA, Small Interfering / pharmacology Specific Pathogen-Free Organisms Xenograft Model Antitumor Assays |
| IF | 2.462 |
| 引用数 | 7 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | EoL-1 cell(RCB0641) |