Knockdown of LncRNA CRNDE suppresses proliferation and P-glycoprotein-mediated multidrug resistance in acute myelocytic leukemia through the Wnt/β-catenin pathway

Biosci Rep. 2020 Jun 26;40(6):BSR20193450. doi: 10.1042/BSR20193450.


Mechanisms involved in non-coding RNAs have been implicated in multidrug resistance (MDR) of acute myeloid leukemia (AML). Long non-coding RNA (lncRNAs) colorectal neoplasia differentially expressed (CRNDE) is reported to be involved in the malignant progression in AML. The purpose of the present study is to explore the roles and potential molecular mechanism of CRNDE in the MDR in AML. In our study, we confirmed that the expression of CRNDE was significantly up-regulated in patients with AML, especially in AML patients after adriamycin (ADR)-based chemotherapy. Spearman correlation analysis showed a positive correlation between the levels of CRNDE and MDR1 in AML patients after ADR-based chemotherapy. Moreover, CRNDE was up-regulated in AML cells, especially in ADR-resistant AML cells. Multidrug resistance protein 1 (MDR1)/p-glycoprotein (P-gp) levels were significantly increased in ADR-resistant AML cells, compared with parental AML cells. CRNDE down-regulation inhibited cell proliferation, promoted apoptosis, reduced Ki67 expression and enhanced cleaved caspase-3 expression in AML and ADR-resistant AML cells. In addition, CRNDE knockdown led to down-regulation of P-gp/MDR1, β-catenin, c-Myc and cyclinD1 expression, and enhanced the drug sensitivity to ADR in ADR-resistant AML cells. In conclusion, knockdown of CRNDE suppresses proliferation and P-gp-mediated MDR in ADR-resistant AML cells via inhibiting the Wnt/β-catenin pathway, suggesting that repression of CRNDE might be a therapeutic target to reverse MDR of ADR-resistant AML cells.

Keywords: LncRNA CRNDE; P-glycoprotein; Wnt/β-catenin pathway; acute myelocytic leukemia; multidrug resistance.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Antibiotics, Antineoplastic / pharmacology*
  • Apoptosis / drug effects
  • Case-Control Studies
  • Cell Proliferation / drug effects*
  • Doxorubicin / pharmacology*
  • Drug Resistance, Neoplasm* / genetics
  • Gene Expression Regulation, Neoplastic
  • HL-60 Cells
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Wnt Signaling Pathway / drug effects*


  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Antibiotics, Antineoplastic
  • CRNDE RNA, human
  • RNA, Long Noncoding
  • Doxorubicin