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LINC01255 combined with BMI1 to regulate human mesenchymal stromal senescence and acute myeloid leukemia cell proliferation through repressing transcription of MCP-1

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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Data availability

All relevant data are available from the authors on request.

Abbreviations

MDS:

Myelodysplastic syndromes

AML:

Acute myeloid leukemia

IPSS:

International prognostic scoring system

IPSS-R:

International prognostic scoring system (IPSS) the revised IPSS

ELN:

European Leukemia Net

ncRNAs:

Non-coding RNAs

miRNAs:

MicroRNAs

piRNAs:

PIWI-interacting RNAs

siRNAs:

Small interfering RNA

snRNAs:

Small nuclear RNAs

snoRNAs:

Small nucleolar RNAs

lncRNAs:

Long non-coding RNAs

BMI1:

B Lymphoma Mo-MLV Insertion Region 1

UCB-MSCs:

Umbilical cord blood-derived MSCs

RIP:

RNA immunoprecipitation

SASP:

Senescence-associated secretory phenotype

MSC:

Human mesenchymal stromal cells

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Funding

This study was supported by Medical and Health Science and Technology Development Project of Shandong (2018WS122), Science and Technology Development Plan (guidance plan) of Taian (2018NS0123), 2019–2020 Chinese Medicine Science and Technology Development Project of Shandong (2019–0343).

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Author notes

  1. Q. Liu and H. Zhang contributed equally.

Authors and Affiliations

  1. Clinical Laboratory, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, China

    Q. Liu

  2. Department of Hematology, The Second Affiliated Hospital of Shandong First Medical University, No. 706, Taishan Street, Taian, 271000, Shandong, China

    J. Dong, J. Li, Y. Duan, Q. Kong & H. Zhang

  3. Research Service Office, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, China

    K. Wang

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  1. Q. Liu
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Contributions

HZ conceived this project; QL, HZ, JD, JL, YD, KW and QK conducted experiments; QL and HZ acquired and analysed data; HZ wrote the manuscript.

Corresponding author

Correspondence to H. Zhang.

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Liu, Q., Dong, J., Li, J. et al. LINC01255 combined with BMI1 to regulate human mesenchymal stromal senescence and acute myeloid leukemia cell proliferation through repressing transcription of MCP-1. Clin Transl Oncol 23, 1105–1116 (2021). https://doi.org/10.1007/s12094-020-02505-5

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