Abstract
Acute leukemia is a hematological malignant tumor. Long non-coding RNA urothelial cancer-associated 1 (UCA1) is involved in the chemo-resistance of diverse cancers, but it is unclear whether UCA1 is associated with the sensitivity of acute leukemia cells to daunorubicin (DNR). DNR (100 nM) was selected for functional analysis. The viability, cell cycle progression, apoptosis, and invasion of treated acute leukemia cells (HL-60 and U-937) were evaluated by cell counting kit-8 (CCK-8) assay, flow cytometry assay, or transwell assay. Protein levels were detected with Western blot analysis. Expression patterns of UCA1 and miR-613 were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between UCA1 and microRNA-613 (miR-613) was verified by dual-luciferase reporter assay. We observed that UCA1 expression was elevated in HL-60 and U-937cells. DNR constrained viability, cell cycle progression, invasion, and facilitated apoptosis of HL-60 and U-937 cells in a dose-dependent manner, but these impacts mediated by DNR were reverted after UCA1 overexpression. MiR-613 was down-regulated in HL-60 and U-937 cells, and UCA1 was verified as a miR-613 sponge. MiR-613 inhibitor reversed DNR treatment-mediated effects on viability, cell cycle progression, apoptosis, and invasion of HL-60 and U-937 cells, but these impacts mediated by miR-613 inhibitor were counteracted after UCA1 inhibition. Notably, the inactivation of the PI3K/AKT pathway caused by DNR treatment was reversed after miR-613 inhibitor introduction, but this influence mediated by miR-613 inhibitor was offset after UCA1 knockdown. In conclusion, UCA1 up-regulation facilitated the resistance of acute leukemia cells to DNR via the PI3K/AKT pathway by sponging miR-613.
Highlights
Acute leukemia is a malignant clonal disease of hematopoietic stem/progenitor cells, which includes acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML) [1]
Flow cytometry assay manifested that DNR treatment promoted cell cycle arrest and apoptosis of HL-60 and U-937 cells with the increase of DNR (Figure 1C,D)
Transwell assay was conducted and the results presented that DNR treatment caused a decrease in the invasion ability of HL-60 and U-937 cells in a dose-dependent manner (Figure 1E)
Summary
Acute leukemia is a malignant clonal disease of hematopoietic stem/progenitor cells, which includes acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML) [1]. The treatment of acute leukemia includes chemotherapy, immunotherapy, radiotherapy, targeted therapy, or stem cell therapy [2]. These treatments improve the prognosis of patients with acute leukemia, chemotherapy resistance remains a major problem [3,4]. Studies have revealed that lncRNAs are involved in many pathological and physiological processes, such as tumorigenesis, organogenesis, cell lineage choice, and tissue homeostasis [6,7,8,9]. Increased researches have revealed that lncRNAs are associated with tumor chemo-resistance [10]. Long non-coding RNA urothelial cancer-associated 1 (UCA1) has been reported to be involved in the occurrence and progression of multiple tumors [11].
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