Acute myeloid leukemia (AML) is a highly heterogeneous disease with a very high mortality rate. In recent years, an increasing number of studies have proven that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) may serve as useful biomarkers in various cancer types. However, the mechanism of LINC01018 and miR-499a-5p in AML requires further investigation. The mRNA expression of LINC01018, miR-499a-5p and PDCD4 in AML tissues and cells was detected using reverse transcription-quantitative polymerase chain reaction. Cell proliferation was measured using Cell Counting kit-8 and EdU assays. Cell apoptosis was monitored via a TUNEL staining assay. Protein expression of PDCD4, Bax and Bcl-2 was measured using western blot analysis. The interaction between PDCD4 and LINC01018 or miR-499a-5p was verified by RNA pull-down, RIP and dual-luciferase reporter assays. LINC01018 and PDCD4 were downregulated in AML, while miR-499a-5p was upregulated. LINC01018-overexpression suppressed AML cell proliferation and induced AML cell apoptosis, while miR-499a-5p transfection reversed these effects. LINC01018 acted as a sponge of miR-499a-5p, and PDCD4 was demonstrated to be targeted by miR-499a-5p. Knockdown of miR-499a-5p suppressed AML cell proliferation and promoted AML cell apoptosis, but silencing PDCD4 abolished this effect. LINC01018 inhibited AML cell growth by modulating PDCD4 through suppression of miR-499a-5p, providing a feasible theoretical basis for the treatment of AML.

Background: To explore the biological effects and potential molecular mechanisms of long non-coding RNA (lncRNA) gastric carcinoma proliferation enhancing transcript 1 (GHET1) in acute myeloid leukemia (AML). Methods: Fluorescence in situ hybridization was performed to determine the location of GHET1. Quantitative polymerase chain reaction (qPCR) was performed to verify RNA expression. GHET1 overexpression and knockdown were achieved by transfection of the expression vector or short hairpin RNA. Western blotting, qPCR, Cell Counting Kit-8 assay, JC-1 staining, and flow cytometry were performed to measure GHET1 function. The dual luciferase reporter assay was performed to confirm the relationship between microRNA 105 (mir-105) and Ras-related protein Rap-2B ( RAP2B ). Results: GHET1 was localized in the nucleus of NB4 cell lines. GHET1 expression was elevated in AML cell lines compared with normal bone marrow mononuclear cells. GHET1 knockdown led to inhibition of proliferation and promoted the differentiation and apoptosis of AML cell lines. Furthermore, GHET1 directly bound to miR-105 and downregulated miR-105 expression. MiR-105 overexpression suppressed proliferation and induced the differentiation and apoptosis of AML cell lines. In addition, RAP2B was confirmed to be a target gene of miR-105 and an inverse correlation was shown between their expression levels in AML cell lines; when miR-105 increased, Rap-2B level decreased and vice versa . Conclusion: This study demonstrated that the GHET1/miR-105/ Rap2B axis may be a critical signaling pathway involved in AML progression.