Silencing LINC00987 ameliorates adriamycin resistance of acute myeloid leukemia via miR-4458/HMGA2 axis

Yue Liu1, Xiao-Ya Zhu2, Li-Li Liao3

  • 1Institute of Biomedicine, Department of Cellular Biology, Jinan University, No. 601 Huangpu Ave West, Shipai Street, Tianhe District, Guangzhou, Guangdong, 510632, China.

Biology Direct
|June 23, 2024
PubMed
Abstract

Insights

LINC00987 promotes Adriamycin resistance in acute myeloid leukemia (AML) by sponging miR-4458 and upregulating HMGA2. Downregulating LINC00987 may offer a new therapeutic strategy for chemoresistant AML.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Acute myeloid leukemia (AML) frequently develops drug resistance, leading to poor patient outcomes.
  • Long non-coding RNAs (lincRNAs) are increasingly recognized for their role in chemoresistance within AML.
  • The specific function of lincRNAs in Adriamycin (ADR) resistance in AML remains largely unknown.

Purpose of the Study:

  • To investigate the role of LINC00987 in Adriamycin (ADR) resistance in acute myeloid leukemia (AML) cells.
  • To elucidate the molecular mechanism by which LINC00987 influences chemoresistance in AML.

Main Methods:

  • Construction of ADR-resistant AML cell lines.
  • Quantification of LINC00987, miRNA, and HMGA2 mRNA expression via qRT-PCR.
  • Assessment of P-GP, BCRP, and HMGA2 protein levels using Western blot.
  • Evaluation of cell proliferation, IC50, colony formation, apoptosis, and xenograft tumor growth.

Main Results:

  • LINC00987 expression is elevated in AML patients and correlates with poorer survival.
  • LINC00987 expression significantly increases in ADR-resistant AML cells.
  • LINC00987 downregulation reduces ADR resistance in vitro and in vivo, while overexpression enhances it.
  • LINC00987 acts as a competing endogenous RNA for miR-4458, leading to HMGA2 upregulation and increased ADR resistance.

Conclusions:

  • LINC00987 downregulation mitigates ADR resistance by enabling miR-4458 to reduce HMGA2 levels.
  • LINC00987 emerges as a potential therapeutic target for overcoming chemoresistance in AML.
  • Targeting the LINC00987/miR-4458/HMGA2 axis could be a promising strategy for treating drug-resistant AML.

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