Frontiers in oncology · 2026
miR-2110 orchestrates ERK-ELK1 transcriptional repression to induce cell-cycle arrest and enhance cytarabine sensitivity in acute myeloid leukemia.
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Li Ya, Chen Ying, Huang Aoshuang, Zhan Yun, Ni Ming, Zhang Fengqi, Xu Shaofei, Li Yanju
Аннотация
INTRODUCTION: Acute myeloid leukemia (AML) remains a heterogeneous hematologic malignancy with frequent therapeutic resistance and relapse. Although miR-2110 is upregulated in AML, its functional role and downstream mechanism remain unclear.
METHODS: Publicly available miRNA-sequencing data were analyzed to identify dysregulated miRNAs in AML. miR-2110 expression was validated in AML cell lines. Functional assays, including CCK-8, EdU incorporation, apoptosis analysis, western blotting, dual-luciferase reporter assays, rescue experiments, Ara-C sensitivity assays, and xenograft experiments, were performed to evaluate the role of miR-2110 and its downstream target.
RESULTS: miR-2110 was upregulated in AML samples and cell lines but exerted tumor-suppressive effects. miR-2110 overexpression inhibited AML cell proliferation, reduced cell-cycle-related protein expression, and promoted apoptosis-related changes. ELK1 was identified and validated as a direct target of miR-2110 through multiple predicted binding sites within its 3'UTR. Restoration of ELK1 partially reversed miR-2110-associated molecular changes, supporting ELK1 as an important downstream mediator. miR-2110 also enhanced Ara-C responsiveness in parental and resistant AML cells, while Ara-C-resistant cells showed reduced miR-2110 and increased ELK1 expression. In vivo, miR-2110 overexpression suppressed xenograft tumor growth without obvious body weight loss.
DISCUSSION: miR-2110 functions as an upregulated but tumor-suppressive miRNA in AML. The miR-2110-ELK1 axis contributes to regulation of AML cell growth, apoptosis-related signaling, and Ara-C responsiveness, providing a potential molecular basis for further investigation of miRNA-mediated therapeutic modulation in AML.
METHODS: Publicly available miRNA-sequencing data were analyzed to identify dysregulated miRNAs in AML. miR-2110 expression was validated in AML cell lines. Functional assays, including CCK-8, EdU incorporation, apoptosis analysis, western blotting, dual-luciferase reporter assays, rescue experiments, Ara-C sensitivity assays, and xenograft experiments, were performed to evaluate the role of miR-2110 and its downstream target.
RESULTS: miR-2110 was upregulated in AML samples and cell lines but exerted tumor-suppressive effects. miR-2110 overexpression inhibited AML cell proliferation, reduced cell-cycle-related protein expression, and promoted apoptosis-related changes. ELK1 was identified and validated as a direct target of miR-2110 through multiple predicted binding sites within its 3'UTR. Restoration of ELK1 partially reversed miR-2110-associated molecular changes, supporting ELK1 as an important downstream mediator. miR-2110 also enhanced Ara-C responsiveness in parental and resistant AML cells, while Ara-C-resistant cells showed reduced miR-2110 and increased ELK1 expression. In vivo, miR-2110 overexpression suppressed xenograft tumor growth without obvious body weight loss.
DISCUSSION: miR-2110 functions as an upregulated but tumor-suppressive miRNA in AML. The miR-2110-ELK1 axis contributes to regulation of AML cell growth, apoptosis-related signaling, and Ara-C responsiveness, providing a potential molecular basis for further investigation of miRNA-mediated therapeutic modulation in AML.