Expression of LOC285758, a potential long non-coding biomarker, is methylation-dependent and correlates with glioma malignancy grade

Abstract

BackgroundIdentifying the early genetic drivers can help diagnose glioma tumours in their early stages, before becoming malignant. However, there is emerging evidence that disturbance of epigenetic mechanisms also contributes to cell’s malignant transformation and cancer progression. Long non-coding RNAs are one of key epigenetic modulators of signalling pathways, since gene expression regulation is one of their canonical mechanisms. The aim of our study was to search new gliomagenesis-specific candidate lncRNAs involved in epigenetic regulation.Patients and methodsWe used a microarray approach to detect expression profiles of epigenetically involved lncRNAs on a set of 12 glioma samples, and selected LOC285758 for further qPCR expression validation on 157 glioma samples of different subtypes. To establish if change in expression is a consequence of epigenetic alterations we determined methylation status of lncRNA’s promoter using MS-HRM. Additionally, we used the MLPA analysis for determining the status of known glioma biomarkers and used them for association analyses.ResultsIn all glioma subtypes levels of LOC285758 were significantly higher in comparison to normal brain reference RNA, and expression was inversely associated with promoter methylation. Expression substantially differs between astrocytoma and oligodendroglioma, and is elevated in higher WHO grades, which also showed loss of methylation.ConclusionsOur study revealed that lncRNA LOC285758 changed expression in glioma is methylation-dependent and methylation correlates with WHO malignancy grade. Methylation is also distinctive between astrocytoma I-III and other glioma subtypes and may thus serve as an additional biomarker in glioma diagnosis.

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.…”

“…AML, which is a highly heterogeneous hematopoietic malignancy with an annual incidence of approximately 3/100 000, remains a great challenge in clinical oncology [3,4]. 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].…”

“…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]. Evidence increasingly showed that abnormal expressions of lncRNAs are highly related to the occurrence and development of various diseases, indicating that lncRNAs can function not only as a typical oncogene, but also as tumor-suppressive genes [8,9].…”

“…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]. Evidence increasingly showed that abnormal expressions of lncRNAs are highly related to the occurrence and development of various diseases, indicating that lncRNAs can function not only as a typical oncogene, but also as tumor-suppressive genes [8,9].…”

“…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.…”