Scholarlink

<p>Acute erythroid leukemia (AEL) is a rare acute myeloid leukemia (AML) subtype that is highly aggressive and is associated with a poor prognosis. Notably, the blockage of erythroid differentiation represents a significant factor in the pathogenesis of erythroleukemia. Prior studies indicated that <i>miR-218</i> inhibited the erythroid differentiation in a chronic myeloid leukemia (CML)-derived erythroleukemia cell line K562. However, functions of <i>miR-218</i> in primary AEL remains to be elucidated. To address this gap, functions of <i>miR-218</i> in HEL cells were evaluated through cell differentiation, cell proliferation, colony formation, cell cycle and cell apoptosis experiments. Subsequently, the targeted downstream genes of <i>miR-218</i> were identified by the transcriptome sequencing and bioinformatic research, of which demonstrated by the dual-luciferase reporter experiment. Finally, the underlying mechanism of <i>miR-218</i> in leukemogenesis was identified by enrichment analysis and was validated by western blot (WB) assays. Intriguingly, enhanced <i>miR-218</i> showed no effect on the erythroid differentiation in HEL cells by determination of the expression of erythroid markers including GATA1, KLF1, TFRC and GYPA. However, <i>miR-218</i> overexpression in HEL cells presented a markedly anti-proliferative and pro-apoptotic effects, inhibited colony formation and G0/G1 arrest. Transcriptome sequencing and bioinformatics analysis revealed that <i>CTNND2</i> as the candidate gene of <i>miR-218</i> within its 3′-untranslated region (3′-UTR) could be bonded by it. Reduced expression level of <i>CTNND2</i> was further demonstrated by quantitative-PCR and WB after <i>miR-218</i> overexpression in HEL cells. Furthermore, the luciferase report assay revealed that the <i>CTNND2</i> production was reduced with its 3′-UTR region was bonded by <i>miR-218</i>. In addition, MAPK signaling pathway was identified and validated as the potential functional pathway involved in leukemogenesis caused by <i>miR-218</i> overexpression in HEL cells. In summary, <i>m</i><i>iR-218</i> exhibits anti-proliferative and pro-apoptotic functions by targeting <i>CTNND2</i> and modulating MAPK signaling in HEL cells, yet it has no impact on the erythroid differentiation process.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

MiR-218 Exhibits Anti-Leukemia Effects by Targeting CTNND2 in Primary Acute Erythroid Leukemia HEL Cells

  • 期刊论文

  • 发表日期：

    2025年3月18日

查看全文
  • Ming-qiang Chu,
  • Ting-juan Zhang,
  • Zi-qi Liu,
  • Qian Yang,
  • Ting-ting Du,
  • Min-jie Zhang,
  • Ye Jin,
  • Yong-jie Cao,
  • Xiang-mei Wen,
  • Zi-jun Xu,
  • Yang-jing Zhao,
  • Jiang Lin,
  • Jun Qian,
  • Jing-dong Zhou

摘要

Acute erythroid leukemia (AEL) is a rare acute myeloid leukemia (AML) subtype that is highly aggressive and is associated with a poor prognosis. Notably, the blockage of erythroid differentiation represents a significant factor in the pathogenesis of erythroleukemia. Prior studies indicated that miR-218 inhibited the erythroid differentiation in a chronic myeloid leukemia (CML)-derived erythroleukemia cell line K562. However, functions of miR-218 in primary AEL remains to be elucidated. To address this gap, functions of miR-218 in HEL cells were evaluated through cell differentiation, cell proliferation, colony formation, cell cycle and cell apoptosis experiments. Subsequently, the targeted downstream genes of miR-218 were identified by the transcriptome sequencing and bioinformatic research, of which demonstrated by the dual-luciferase reporter experiment. Finally, the underlying mechanism of miR-218 in leukemogenesis was identified by enrichment analysis and was validated by western blot (WB) assays. Intriguingly, enhanced miR-218 showed no effect on the erythroid differentiation in HEL cells by determination of the expression of erythroid markers including GATA1, KLF1, TFRC and GYPA. However, miR-218 overexpression in HEL cells presented a markedly anti-proliferative and pro-apoptotic effects, inhibited colony formation and G0/G1 arrest. Transcriptome sequencing and bioinformatics analysis revealed that CTNND2 as the candidate gene of miR-218 within its 3′-untranslated region (3′-UTR) could be bonded by it. Reduced expression level of CTNND2 was further demonstrated by quantitative-PCR and WB after miR-218 overexpression in HEL cells. Furthermore, the luciferase report assay revealed that the CTNND2 production was reduced with its 3′-UTR region was bonded by miR-218. In addition, MAPK signaling pathway was identified and validated as the potential functional pathway involved in leukemogenesis caused by miR-218 overexpression in HEL cells. In summary, miR-218 exhibits anti-proliferative and pro-apoptotic functions by targeting CTNND2 and modulating MAPK signaling in HEL cells, yet it has no impact on the erythroid differentiation process.