MALAT1 knockdown inhibits proliferation and enhances cytarabine chemosensitivity by upregulating miR-96 in acute myeloid leukemia cells.

Drug resistance remains a major cause of relapse and therapeutic failure in acute myeloid leukemia (AML). Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been documented to act as an oncogene and is frequently highly expressed in human cancers including AML. However, the function and molecular mechanism of MALAT1 in regulating cytarabine (Ara-C) resistance of AML are largely unknown. The expressions of MALAT1 and miR-96 in AML patients and healthy controls were examined by qRT-PCR. CCK-8 and flow cytometry assay were performed to assess the proliferation and apoptosis of AML cells. The interaction between MALAT1 and miR-96 was investigated by luciferase reporter assay. We found that MALAT1 was upregulated while miR-96 was downregulated in AML patients compared with healthy controls. A negative correlation between MALAT1 and miR-96 expressions was observed in AML patients. Knockdown of MALAT1 inhibited the proliferation, induced apoptosis, and enhanced Ara-C sensitivity of AML cells. Additionally, MALAT1 suppressed miR-96 expression by acting as a molecular sponge of miR-96 in AML cells. miR-96 downregulation abolished the effects of MALAT1 knockdown on the proliferation, apoptosis, Ara-C sensitivity in AML cells. In conclusion, MALAT1 knockdown inhibited proliferation, promoted apoptosis and enhanced Ara-C sensitivity in AML cells by upregulating miR-96, providing novel insights into the critical role of MALAT1 as a miRNA sponge in AML.