2. Academic Validation
  3. LncRNA SNHG5 induces CAFs-like phenotype and autophagy of AML-MSCs via PTBP1/ATG5 axis to confer chemoresistance of AML cells

LncRNA SNHG5 induces CAFs-like phenotype and autophagy of AML-MSCs via PTBP1/ATG5 axis to confer chemoresistance of AML cells

  • Cell Signal. 2025 Apr:128:111625. doi: 10.1016/j.cellsig.2025.111625.
Yuan Song 1,  Lili Hu 2,  Jing Cheng 1,  Zhenjiang Li 1,  Jifu Zheng 3
Affiliations

Affiliations

  • 1 Department of Hematology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Jiangxi Provincial Key Laboratory of Hematological Diseases, Nanchang 330006, Jiangxi Province, People's Republic of China.
  • 2 Department of Nephrology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, People's Republic of China.
  • 3 Department of Hematology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Jiangxi Provincial Key Laboratory of Hematological Diseases, Nanchang 330006, Jiangxi Province, People's Republic of China. Electronic address: ncjeff@163.com.
PMID: 39864537 DOI: 10.1016/j.cellsig.2025.111625
Abstract

Background: Acute myeloid leukemia (AML) is still a threaten to human health due to its high occurrence and poor prognosis. Mesenchymal stem cells (MSCs) in bone marrow microenvironment (BMM) play a critical role in the development of AML. This study elucidated the interaction between MSCs and AML cells and its underlying mechanism.

Method: MSCs were isolated, identified, and co-cultured with AML cells. qRT-PCR, Western blotting and immunofluorescence were used to determine molecule expression. Cell viability and Apoptosis were determined by CCK-8 and flow cytometry. Exosomes were isolated and characterized, and PKH26 was used for monitoring exosome internalization. RNA-FISH was used to determine the localization of SNHG5. RIP, RNA-pull down and ChIP assays were used to evaluate the molecular interaction.

Results: SNHG5 expression was up-regulated and positively correlated with cancer-associated fibroblasts (CAFs)-related biomarkers in AML-MSCs. AML cells-derived exosomes delivered SNHG5 to enhance its expression in MSCs. SNHG5 overexpression induced CAFs-like phenotype and Autophagy in HD-MSCs that led to daunorubicin resistance of AML cells. Mechanistically, SNHG5 stabilized Autophagy related 5 (ATG5) mRNA by interaction with polypyrimidine tract-binding protein 1 (PTBP1).

Conclusion: AML cells-derived exosomal lncRNA SNHG5 triggered CAFs-like phenotype and Autophagy of AML-MSCs via interaction with PTBP1 to increase ATG5 mRNA stability, thereby leading to chemoresistance of AML cells.

Keywords

AML; ATG5; MSCs; PTBP1; lncRNA SNHG5.

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