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miR-218 inhibits acute promyelocytic leukemia cell growth by targeting BMI-1
Yan Wang1, Hai-Hong Sun2, Ming-Hua Sui3
1Department of Hematology, Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.
Abstract:
Acute promyelocytic leukemia (APL) is a subtype of acute myelocytic leukemia. Previous studies have reported a number of functions and therapeutic roles of microRNAs (miRs) in APL, and have suggested that miR-218 acts as a tumor suppressor in a number of types of human cancer; however, its role in APL remains unclear. In the present study, the expression of miR-218 and its effects on the viability and proliferation of HL-60 cells was investigated. Reverse transcription-quantitative polymerase chain reaction analysis demonstrated that miR-218 was frequently downregulated in APL marrow tissues compared with normal marrow tissues. Overexpression of miR-218 significantly inhibited cell proliferation, arrested the cell cycle in the G0/G1 phase and induced apoptosis. In addition, B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) mRNA expression was negatively associated with miR-218 expression; BMI-1 mRNA and protein expression were downregulated following transfection with miR-218 mimic. These results indicate that miR-218 functions as tumor suppressor in APL, and the miR-218/BMI-1 signaling axis may be a potential novel diagnostic marker and therapeutic target for the treatment of APL.
Insights
MicroRNA-218 (miR-218) acts as a tumor suppressor in acute promyelocytic leukemia (APL). Its downregulation in APL suggests the miR-218/BMI-1 axis as a potential therapeutic target.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia.
- MicroRNAs (miRs) have demonstrated therapeutic potential in APL.
- The specific role of miR-218 in APL pathogenesis was previously undefined.
Purpose of the Study:
- To investigate the expression levels of miR-218 in APL.
- To determine the functional impact of miR-218 on HL-60 cell viability and proliferation.
- To elucidate the relationship between miR-218 and BMI-1 in APL.
Main Methods:
- Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to assess miR-218 expression.
- HL-60 cells were utilized to study the effects of miR-218 overexpression.
- Western blotting and RT-qPCR were employed to analyze BMI-1 expression.
Main Results:
- miR-218 was found to be significantly downregulated in APL marrow tissues compared to normal tissues.
- Overexpression of miR-218 suppressed HL-60 cell proliferation, induced G0/G1 cell cycle arrest, and promoted apoptosis.
- miR-218 expression negatively correlated with BMI-1 (B-cell-specific Moloney murine leukemia virus integration site 1) mRNA and protein levels, which were reduced upon miR-218 mimic transfection.
Conclusions:
- miR-218 functions as a tumor suppressor in APL.
- The miR-218/BMI-1 signaling pathway represents a potential diagnostic biomarker and therapeutic target for APL treatment.
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