Clinical Laboratory, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, China.
Department of Hematology, The Second Affiliated Hospital of Shandong First Medical University, No. 706, Taishan Street, Taian, 271000, Shandong, China.
Clin Transl Oncol. 2021 Jun;23(6):1105-1116. doi: 10.1007/s12094-020-02505-5. Epub 2021 Jan 6.
Long non-coding RNAs (lncRNAs) govern fundamental biochemical and cellular biology processes, for example, participate in chromatin remodeling, imprinting, splicing, transcriptional regulation and translation. Dysregulation of lncRNA expression is act as a feature of various diseases and cancers, including hematopoietic malignancies. However, the clinical relevance of myelodysplastic syndrome (MDS) and acute myeloid leukemia preceded by MDS (MDS-AML) requires further research. Recently, lncRNAs have been demonstrated, which play an important role in hematopoiesis, thus, to further finding more functional lncRNA seemed particularly important.
Western blotting, real-time PCR, RNA-pulldown, RIP (RNA immunoprecipitation), Chromatin immunoprecipitation (ChIP), cellular compartments extraction assays, SA-β-gal staining, lentivirus transfection, cell viability assay and cell proliferation assays were used to examine the relationship between lncRNA LINC01255 and its regulation of p53-p21 pathway in human mesenchymal stromal and acute myeloid leukemia cells.
LncRNA LINC01255 is highly expressed in bone marrow cells of AML patients, CD34+ cells of MDS-AML patients and AML cell lines and the higher expression of LINC01255 is associated with poor survival rate of AML patients. LINC01255 can interact with BMI1 and repress the transcription of MCP-1 to active p53-p21 pathway, thus inhibiting the senescence of human mesenchymal stromal and proliferation of acute myeloid leukemia cell.
We discovered a novel functional lncRNA LINC01255, which can regulate the senescence of human mesenchymal stromal and the proliferation of acute myeloid leukemia cell through inhibiting the transcription of MCP-1.
长链非编码 RNA（lncRNA）调控基本的生化和细胞生物学过程，例如参与染色质重塑、印迹、剪接、转录调控和翻译。lncRNA 表达失调可作为各种疾病和癌症（包括血液恶性肿瘤）的特征。然而，骨髓增生异常综合征（MDS）和 MDS 前急性髓系白血病（MDS-AML）的临床相关性需要进一步研究。最近，lncRNA 已被证明在造血中发挥重要作用，因此，进一步寻找更多功能的 lncRNA 似乎尤为重要。
采用 Western blot、实时 PCR、RNA 下拉、RIP（RNA 免疫沉淀）、染色质免疫沉淀（ChIP）、细胞区室提取测定、SA-β-半乳糖苷染色、慢病毒转染、细胞活力测定和细胞增殖测定等方法，研究 lncRNA LINC01255 与骨髓间充质基质和急性髓系白血病细胞中 p53-p21 通路的关系及其调控作用。
lncRNA LINC01255 在 AML 患者骨髓细胞、MDS-AML 患者 CD34+细胞和 AML 细胞系中高表达，LINC01255 的高表达与 AML 患者的生存率降低相关。LINC01255 可与 BMI1 相互作用，抑制 MCP-1 的转录，激活 p53-p21 通路，从而抑制人骨髓间充质基质的衰老和急性髓系白血病细胞的增殖。
我们发现了一种新的功能 lncRNA LINC01255，它可以通过抑制 MCP-1 的转录来调节人骨髓间充质基质的衰老和急性髓系白血病细胞的增殖。
