SNHG5 was aberrantly overexpressed in AML samples compared to controls.
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SNHG5 promoted chemotherapy resistance in AML.
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SNHG5 regulated chemotherapy resistance via miR-32/DNAJB9 axis in AML.
Abstract
Background
Acute myeloid leukemia (AML) is a common hematopoietic malignancy with invasive activity. Drug resistance greatly contributes to the poor efficacy of chemotherapy in AML treatment. Recent research indicates that long non-coding RNAs (LncRNAs) regulates chemotherapy resistance in malignancy.
Methods
Microarray analysis was used to screen out AML related genes, and interaction between small nucleolar RNA host gene 5(SNHG5) and miR-32, as well as that between miR-32 and DNAJB9. Quantitative real-time PCR (qRT-PCR) and In situ hybridization(ISH) were used to determine the expression levels of SNHG5, miR-32 and DNAJB9 mRNA in AML cell lines and clinic samples. Western blot was performed to detect protein expression levels. After being treated with varying concentrations of Adriamycin(ADM), cell viability was evaluated using a cell counting kit-8(CCK8).
Results
We carried out a genome-wide LncRNA expression study and found SNHG5 aberrantly overexpressed in AML comparing to the donors. Knock-down of SNHG5 promoted sensitivity of AML cells to chemotherapy. In addition, miR-32 was identified as the downstream target of SNHG5 and miR-32 inhibitor abrogated the inhibiting effects of downregulated SNHG5 on AML cell viability. Furthermore, inhibited SNHG5 decreased DNAJB9 expression levels by sponging miR-32. The SNHG5/miR-32/DNAJB9 axis targeted autophagy to regulate chemotherapy resistance.
Conclusion
SHNG5 regulates chemotherapy resistance by targeting the miR-32/DNAJB9 axis in acute myeloid leukemia, which provided a novel potential target for AML and revealed an important mechanism of chemotherapy resistance.
