Roles of hsa-miR-12462 and SLC9A1 in acute myeloid leukemia

Abstract

MicroRNAs (miRNAs) play important roles in cell proliferation, differentiation, and survival and may be useful for acute myeloid leukemia (AML) diagnosis and prognosis. In this study, we defined a novel miRNA, hsa-miR-12462, through small RNA sequencing of the bone marrow (BM) cells from 128 AML patients. Overexpression of hsa-miR-12462 in AML cells (U937 and HL-60) significantly decreased their growth rate when compared with those of the wild-type and MOCK controls. In a xenograft mouse model, tumor weight and size in the mice bearing the U937 cells with hsa-miR-12462 overexpression were significantly reduced when compared with those bearing the mock cells. The AML cells overexpressing hsa-miR-12462 had increased sensitivity to cytarabine chemotherapy. Combining the data from the MiRDB, an online microRNA database (http://mirdb.org), with the RNA-sequencing results, SLC9A1 was predicted to be one of the targets of hsa-miR-12462. hsa-miR-12462 was further confirmed to bind exclusively to the 3′UTR of SLC9A1 in U937 cells, leading to downregulation of SLC9A1. In summary, a higher level of hsa-miR-12462 in AML cells is associated with increased sensitivity to cytarabine chemotherapy via downregulation of SLC9A1.

GLI1 reduces drug sensitivity by regulating cell cycle through PI3K/AKT/GSK3/CDK pathway in acute myeloid leukemia

“…New targets and therapeutic approaches are needed. Among them, targeted therapy has proven to be a promising research area for AML treatment 2 – 4 .…”

Circular RNA circ_0004277 Inhibits Acute Myeloid Leukemia Progression Through MicroRNA-134-5p / Single stranded DNA binding protein 2

“…MiR-34c-5p is remarkably down-regulated in AML stem cells, and its under-expression is closely correlated with unfavorable prognosis and unfavorable treatment response in AML patients; in addition, miR-34c-5p overexpression induces senescence of AML stem cells in immunodeficient mice in vitro , prevents leukemogenesis and enhances eradication of AML stem cells [ 24 ]. Another study reports that miR-12462 overexpression promotes the sensitivity of AML cells to cytarabine chemotherapy and restrains the development of tumors in xenograft mice [ 25 ]. In this work, we confirm the targeting relationship between miR-134-5p and circ_0004277.…”

miR-342-3p Inhibits Acute Myeloid Leukemia Progression by Targeting SOX12

“…Evidence in recent years has revealed that miRNAs are strongly linked to AML occurrence and development and play a crucial regulatory role in AML occurrence by regulating their target genes. There is a study indicating that in AML, miR-12462 is low-expressed and inhibits AML cell growth both in vivo and in vitro and enhances AML cell chemotherapy sensitivity via targeting SLC9A1, thus playing a tumor-suppressing role [ 29 ]. miR-212-5p keeps at a low level in AML cells, and overexpressing miR-212-5p can suppress AML cell growth and promote apoptosis [ 30 ].…”