LINC01234通过调控IGF2BP1 c-Myc对急性髓系白血病细胞增殖 侵袭 迁移的影响

Effects of LINC01234 on proliferation, invasion, and migration of acute myeloid leukemia cells by regulating IGF2BP1/c-Myc

    摘要
  • 摘要:
      目的  探讨LINC01234通过调控胰岛素样生长因子2 mRNA结合蛋白1（insulin-like growth factor 2 mRNA binding protein 1，IGF2BP1）/c-Myc对急性髓系白血病（acute myeloid leukemia，AML）细胞增殖、侵袭、迁移的影响。
      方法  分析2019年3月至2021年9月在湖北省恩施州中心医院确诊的31例AML患者和在本院体检的24例健康志愿者的外周血标本。通过实时定量PCR（real-time quantitative PCR，qRT-PCR）检测分析LINC01234在AML标本和细胞系（MV-4-11、NB4、KG-1、THP-1、HL-60）中的表达模式。HL-60细胞随机记为空白对照（blank control，BC）组、sh-control组、sh-LINC01234组、sh-LINC01234+pcDNA-control组、 sh-LINC01234+pcDNA-c-Myc组。qRT-PCR检测细胞中LINC01234、IGF2BP1和c-Myc的表达。细胞计数试剂盒-8实验、transwell迁移和侵袭实验用于细胞增殖能力、细胞侵袭和迁移功能的研究。通过RNA免疫沉淀和RNA pull-down实验证实LINC01234、IGF2BP1和c-Myc在AML细胞中的调节相关性。
      结果  与健康志愿者标本和人骨髓基质细胞HS-5相比，LINC01234在AML标本和5种细胞系中表达均升高（P<0.05）。sh-LINC01234下调HL-60细胞中LINC01234水平后，OD值显著降低，侵袭、迁移细胞数目显著减少（P<0.05）。LINC01234结合IGF2BP1，促进IGF2BP1与c-Myc mRNA的相互作用，从而促进c-Myc mRNA的稳定性（P<0.05）。c-Myc过表达逆转了LINC01234沉默对HL-60细胞增殖、转移的阻碍作用（P<0.05）。
      结论  LINC01234是一种新型AML相关的lncRNA，通过竞争性结合IGF2BP1促进c-Myc mRNA的稳定性，进而促进AML细胞增殖、侵袭和迁移。

     

    Abstract:
      Objective  To investigate the impact of LINC01234 on the proliferation, invasion, and migration of acute myeloid leukemia (AML) cells by regulating insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1)/c-Myc expression.
      Methods  Peripheral blood samples were collected from 31 AML patients and 24 healthy volunteers who underwent physical examination at Enshi Center Hospital from March 2019 to September 2021. The expression pattern of LINC01234 in AML specimens and five cell lines, MV-4-11, NB4, KG-1, THP-1, and HL-60, was analyzed using real-time quantitative PCR (qRT-PCR). HL-60 cells were randomly selected for use in preparing the blank control (BC) group, sh-control group, sh-LINC01234 group, sh-LINC01234+pcDNA-control group, and sh-LINC01234 +pcDNA-c-Myc group. qRT-PCR was performed to measure the expression of LINC01234, IGF2BP1, and c-Myc in the cells. Cell counting kit-8 assay and transwell migration and invasion assay were performed to assess cell proliferation ability and cell migration and invasion, respectively. RNA immunoprecipitation and RNA pull-down experiments were performed to confirm the regulatory relevance of LINC01234, IGF2BP1, and c-Myc in AML cells.
      Results  LINC01234 expression was higher in AML specimens and the five cell lines than in specimens from healthy volunteers and human bone marrow stromal cells HS-5 (P<0.05). After LINC01234 expression was downregulated by sh-LINC01234 in HL-60 cells, the OD value and the numbers of invasive and migrating cells were significantly reduced (P<0.05). LINC01234 bound to IGF2BP1 and promoted the interaction between IGF2BP1 and c-Myc mRNA, thereby improving the stability of c-Myc mRNA (P<0.05). Overexpression of c-Myc reversed the decrease in proliferation and metastasis of HL-60 cells caused by LINC01234 silencing (P<0.05).
      Conclusions  LINC01234 is a novel AML-related lncRNA that promotes the stability of c-Myc mRNA by competitively binding to IGF2BP1, thereby promoting proliferation, invasion, and migration of AML cells.

     

    • HTML全文
    • 参考文献(25)
    • 相关文章
    • 施引文献
  • 资源附件(0)

/

返回文章
返回