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

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.