title: The role of long noncoding RNA HOTAIR in the acquired multidrug resistance to imatinib in chronic myeloid leukemia cells.
abstract: OBJECTIVE
  Imatinib, a breakpoint cluster region-Abelson murine leukemia tyrosine kinase inhibitor, has revolutionized the treatment of chronic myelogenous leukemia (CML). However, the development of multidrug resistance (MDR) limits the clinical application of imatinib. In this study, we aimed to investigate the mechanisms of long noncoding RNA (lncRNA) HOTAIR in CML resistance to imatinib.
  
  
  METHODS
  Thirty-four CML patients were divided into multidrug resistance protein 1 (MRP1)-low and MRP1-high groups according to the median expression. Real-time PCR (qPCR) was used to detect the expression of lncRNA HOTAIR in CML patients, and MTT assay and flow cytometry assay were employed to detect the biological function of silencing lncRNA HOTAIR on the cell survival rate and apoptotic rate. An imatinib-resistant human CML cell line K562 (K562-R) was established, and western blot was used to detect the impact of lncRNA HOTAIR on the activation of PI3K/Akt signaling pathway.
  
  
  RESULTS
  Our results showed that lncRNA HOTAIR was greatly upregulated in the MRP1-high patients as well as in the K562-imatinib-resistant cells compared with control. Knockdown of HOTAIR expression downregulated the MRP1 expression levels in the K562-imatinib cells and resulted in higher sensitivity to the imatinib treatment. In addition, the activation of PI3K/Akt was greatly attenuated when HOTAIR was knocked down in K562-imatinib cells.
  
  
  CONCLUSIONS
  These data suggest that the knockdown of HOTAIR may play a crucial role in improving acquired resistance to imatinib in CML K562-R cells via PI3K/Akt pathway.
  
  
  CONCLUSIONS
  LncRNA HOTAIR modulates CML cell MDR in a PI3K/Akt-dependent way.
authors.affiliation: a Department of Hematology , Shandong Provincial Hospital Affiliated to Shandong University , Jinan , China.|b Department of Hematology , The Affiliated Hospital of Weifang Medical University , Weifang , Shandong , China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Wang
authors.affiliation: c Department of Hematology and Blood and Marrow Transplantation , Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy , Tianjin , China.|d Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College , Tianjin , China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: b Department of Hematology , The Affiliated Hospital of Weifang Medical University , Weifang , Shandong , China.
authors.forename: Shusen
authors.initials: S
authors.lastname: Tang
authors.affiliation: b Department of Hematology , The Affiliated Hospital of Weifang Medical University , Weifang , Shandong , China.
authors.forename: Meifang
authors.initials: M
authors.lastname: Li
authors.affiliation: b Department of Hematology , The Affiliated Hospital of Weifang Medical University , Weifang , Shandong , China.
authors.forename: Anhua
authors.initials: A
authors.lastname: Feng
authors.affiliation: b Department of Hematology , The Affiliated Hospital of Weifang Medical University , Weifang , Shandong , China.
authors.forename: Lili
authors.initials: L
authors.lastname: Qin
authors.affiliation: e Department of Pathophysiology , Tianjin Medical University , Heping, Tianjin , China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: a Department of Hematology , Shandong Provincial Hospital Affiliated to Shandong University , Jinan , China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology*; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000096:biosynthesis / Q000235:genetics*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D000068877:Imatinib Mesylate; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D019869:Phosphatidylinositol 3-Kinases; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D062085:RNA, Long Noncoding; C561566:HOTAIR long untranslated RNA, human; C421109:multidrug resistance-associated protein 1
keywords: Chronic myeloid leukemia; PI3K/Akt pathway; imatinib resistance; long noncoding RNA HOTAIR