Genome-wide characterization of lncRNAs in acute myeloid leukemia

Abstract

Long noncoding RNAs (lncRNAs) are a large family of noncoding RNAs that play a critical role in various normal bioprocesses as well as tumorigenesis. However, the expression patterns and biological functions of lncRNAs in acute leukemia have not been well studied. Here, we performed transcriptome-wide lncRNA expression profiling of acute myeloid leukemia (AML) patient samples, along with non-leukemia control hematopoietic samples. We found that lncRNAs were differentially expressed in AML samples relative to control samples. Notably, we identified that lncRNAs upregulated in AML (relative to the control samples) are associated with a lower degree of DNA methylation and a higher ratio of being bound by transcription factors such as SP1, STAT4, ATF-2 and ELK-1 compared with those downregulated in AML. Moreover, an enrichment of H3K4me3 and a depletion of H3K27me3 were observed in upregulated lncRNAs in AML. Expression patterns of three types of lncRNAs (antisense, enhancer and intergenic lncRNAs) have previously been characterized. Of the identified lncRNAs, we found that high expression level lncRNA LOC285758 is associated with the poor prognosis in AML patients. Furthermore, we found that LOC285758 regulates proliferation of AML cell lines by enhancing the expression of HDAC2, a key factor in carcinogenesis. Collectively, our study depicts a landscape of important lncRNAs in AML and provides novel potential therapeutic targets and prognostic markers for AML treatment.

The long non‐coding RNA LOC285758 promotes invasion of acute myeloid leukemia cells by down‐regulating miR‐204‐5p

“…Transfection lncRNA LOC285758 overexpression vector (LOC285758; lnc6180620115353-1-5), negative control (NC; lnc6N0000 002-1-10), miR-204-5p mimics (Mimic; miR10022693- [1][2][3][4][5] and Mimic control (miR01102-1-1) were purchased from RIBOBIO (Guangzhou, China). RNase-free H 2 O (ST876; Beyotime, Shanghai, China) was used to dilute LOC285758, NC, Mimic and Mimic control to 20 lM and was stored at À20°C for later use.…”

“…The data also showed that increased LOC285758 expression could effectively suppress the earlier effects of miR-204-5p on AML cells. Our findings suggest that targeting of miR-204-5p by LOC285758 promotes the cell viability and invasion of AML cells, and thus LOC285758 may have potential as a therapeutic target for AML treatment.Acute myeloid leukemia (AML) is the second most common type of leukemia worldwide [1,2]. The latest statistics revealed that the cure rate of AML in the young is 35%, whereas in the aged it is 15% by modern treatment strategies [3].…”

“…The heterogeneity is also reflected in the lack of knowledge about detailed mechanisms of tumor formation and progression, resulting in less accurate classification and increased difficulty of deciding the appropriate treatment plan [5]. In total, 60-80% of AML pathogenesis is associated with a chromosome translocation in somatic cells [1,6]. The dismal prognosis of AML motivates researchers to identify new genetic factors and investigate molecular mechanisms involved in AML pathogenesis, which may also contribute to the development of new therapeutic approaches and improvement of AML prognosis.Long noncoding RNAs (lncRNAs) are a class of noncoding RNAs that share many features with protein-coding RNAs (mRNAs) but lack open reading frame and are less conserved in their sequences and low expressed [5,7].…”

“…Acute myeloid leukemia (AML) is the second most common type of leukemia worldwide [1,2]. The latest statistics revealed that the cure rate of AML in the young is 35%, whereas in the aged it is 15% by modern treatment strategies [3].…”

“…In addition, recent studies have proved that lncRNAs not only play a vital role in AML, but also served as biomarkers for early screening, diagnosis and treatment of AML [10,11]; for example, lncRNA HOXB-AS3 was found to promote AML cell proliferation [12], lncRNA H22954 showed an inhibitory effect on AML cell growth via regulating Bcl-2 family [13], and lncRNA PANDAR was correlated with a poor prognosis of AML [14]. In addition, it was reported that lncRNA LOC285758 was high expressed in glioma cells in comparison with healthy brain cells and was negatively associated with promoter methylation in glioma [5], but positively associated with AML cell proliferation [1]. However, the specific effects and mechanisms underlying LOC285758 in AML still need to be further investigated.…”