A long non-coding RNA signature in glioblastoma multiforme predicts survival

Zhang, Xiaoqin; Sun, Stella; Lam, Kwok Fai; Kiang, Karrie Mei-Yee; Pu, Jenny Kan-Suen; Ho, Amy S.W.; Lui, WM; Fung, C. F.; Wong, Thian‐Sze; Leung, Gilberto Ka Kit

doi:10.1016/j.nbd.2013.05.011

Cited by 190 publications

(172 citation statements)

References 55 publications

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“…Existing company and university databases that are currently not being investigated should be explored. Although the lncRNA data profile is large, the mining approach has been demonstrated to be effective when using a proper algorithm (30). In addition, when using data mining for medical research, the dataset should be large and confirmed as reliable.…”

Section: Discussionmentioning

confidence: 99%

The long non-coding RNA HOTAIR is upregulated in endometrial carcinoma and correlates with poor prognosis

Bao

et al. 2013

International Journal of Molecular Medicine

100

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Abstract. Long non-coding RNAs (lncRNAs) are emerging as key molecules in human cancer. Homeobox (HOX) transcript antisense intergenic RNA (HOTAIR), a long non-coding RNA (lncRNA), is associated with a variety of human cancers, such as breast, liver and lung cancer. However, whether HOTAIR can function as a molecular marker in endometrial carcinoma (EC) remains unknown. In the present study, the expression of HOTAIR in 66 EC tissues from patients with EC and 30 normal tissues from healthy age-matched control subjects was determined using quantitative reverse transcription PCR. Furthermore, using in situ hybridization, we measured HOTAIR expression in 129 formalin-fixed paraffin-embedded (FFPE) tissue sections, which included 96 tissues that matched the frozen cases, 21 other EC tissues and 12 atypical hyperplasia tissues. Correlations between HOTAIR expression and the clinicopathological characteristics of patients were analyzed. Our results revealed that HOTAIR expression in the EC tissues was significantly upregulated compared with normal tissues (p<0.001). In addition, we observed a significant association between HOTAIR expression and the EC grade (p<0.05) and lymph node metastasis (p<0.05). Moreover, in the FFPE tissues, but not the frozen tissues, we found that a higher HOTAIR expression also correlated with the depth of myometrial invasion (p=0.019) and lymphovascular space invasion (p=0.015). More importantly, patients with a higher HOTAIR expression showed significantly poorer overall survival than those with lower HOTAIR expression (p<0.05). In conclusion, our results suggest that a high expression of HOTAIR is involved in the progression of cancer and may be a novel biomarker of poor prognosis in patients with EC. IntroductionEndometrial carcinoma (EC) is one of the most common malignancies of the female reproductive system in Western countries. In 2013, an estimated 49,500 new cases and 8,200 deaths due to EC are expected in the USA (1). With the increase in obesity and the decrease in physical activity, the incidence of EC is rising and shows a trend in younger women (2). EC is usually classified into two types to determine the risk of metastasis and recurrence (3). Generally, type I endometrioid endometrial carcinomas (EECs) have a good prognosis and account for 80-85% of the total cases of EC. By contrast, type II non-EECs are often associated with a worse outcome (3,4). However, the prognostic value of this classification is unsatisfactory, as approximately 20% of type I tumors recur, whereas 50% of type II tumors recur (5). A number of previous studies have demonstrated the utility of molecular alterations as prognostic markers, including p53 (6), phosphatase and tensin homolog (PTEN) (7) and ; however, their value is limited (9). Thus, a deeper understanding of the molecular mechanisms responsible for EC is required for risk stratification and a clinical decision regarding individualized treatment strategies.Recent studies have indicated that only 2% of transcripts are protein-coding RNAs, and ...

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Section: Discussionmentioning

confidence: 99%

The long non-coding RNA HOTAIR is upregulated in endometrial carcinoma and correlates with poor prognosis

Bao

et al. 2013

International Journal of Molecular Medicine

100

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“…Currently, a variety of large-scale genomic studies, such as TCGA, are being used to investigate the abnormal expression profiles of lncRNAs in tumor; 97 however, the molecular nature of most lncRNAs remains poorly characterized. Due to their complicated structural characteristics, tissue-specific expression, and specific temporal and spatial expression patterns, the detailed functions and mechanisms of one lncRNA may be significantly different in different tumors.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

Pan

2014

Modern Pathology

102

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Long non-coding RNAs (lncRNAs) are a class of newly identified non-coding RNA molecules that are emerging as key regulators of tumor initiation and development. Colorectal cancer (CRC) remains a major health problem worldwide, and there remains a need to further refine the current screening approaches as well as provide tailored diagnostic and therapeutic approaches. Multiple dysregulated lncRNAs participate in tumorigenesis through a variety of molecular mechanisms, and various regulatory factors frequently contribute to the aberrant expression of lncRNAs in CRC, thereby allowing malignant transformation. Additionally, the association of dysregulated lncRNAs with specific developmental stages and clinical outcomes indicates their potential as strong diagnostic and prognostic predictors as well as therapeutic targets. Here we provide a brief overview of the known functions of CRC-associated lncRNAs, describe some potential molecular mechanisms that underlie changes in lncRNA expression in CRC, and attempt to uncover their clinical and therapeutic potential. Keywords: colorectal cancer; diagnosis; dysregulation; long non-coding RNA; prognosis High-throughput genome-scale studies have demonstrated that more than 93% of the DNA sequences in the human genome are actively transcribed. 1 However, only approximately 5-10% of the sequences are stably transcribed into mRNA or non-coding RNA (ncRNA). Genome tiling arrays have revealed that the amount of non-coding sequence is at least four times larger than the amount of coding sequence, which indicates that only 1% of the human genome is composed of protein-coding genes and the remaining 4-9% is transcribed into ncRNAs. 2 Therefore, ncRNAs constitute a very large proportion of the total RNA molecules.The function and clinical significance of short regulatory ncRNAs, such as microRNAs (miRNAs) and small interfering RNAs (siRNAs), were elucidated first, 3 and the regulatory roles of miRNAs have been broadly recognized in almost all physiological and pathological processes in the body, including carcinogenesis. 4 For example, we previously reported that MIR95 promotes cell proliferation and targets sorting nexin 1 in human colorectal carcinoma; 5 moreover, in colorectal cancer (CRC) patients, the plasma levels of MIR29a and MIR92a are significantly upregulated and the plasma levels of MIR601 and MIR760 are significantly downregulated; thus the levels of these miRNAs have good diagnostic value for CRC screening. 6,7 According to their transcript size, ncRNAs are grouped into two major classes: (i) small ncRNAs with transcripts o200 nucleotides (nt; eg, aforementioned siRNAs and miRNAs, Piwi-interacting RNAs, and some retrotransposon-derived RNAs) and (ii) long non-coding RNAs (lncRNAs), this class includes five broad categories: sense, antisense, bidirectional, intronic, and intergenic, based on the proximity between neighboring transcripts. 8 For a time, lncRNAs was commonly defined as a proteincoding transcripts that is 4200 nt. 9 However, this definition is arbitrary and ...

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“…Accumulating evidence has shown that lncRNAs can drive carcinogenesis by promoting cell proliferation through the regulation of cell cycle and apoptosis (17,19,45). Studies have found that lncRNAs can be used in predicting survival rates in patients with glioma (46), and are potential biomarkers and therapeutic targets for glioma (47,48). However, the roles of lncRNAs in glioma remain to be fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA RP5-833A20.1 inhibits proliferation, metastasis and cell cycle progression by suppressing the expression of NFIA in U251 cells

Kang

Nie

et al. 2016

Molecular Medicine Reports

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Abstract. Early reports suggest that nuclear factor IA (NFIA) is important in the pathogenesis of glioma. Our previous study demonstrated that the long non-coding RNA (lncRNA), RP5-833A20.1, suppressed the expression of NFIA in THP-1 macrophage-derived foam cells. However, the effect and possible mechanism of RP5-833A20.1 on glioma remains to be fully elucidated, and whether the NFIA-dependent pathway is involved in its progression has not been investigated. In the present study, the mechanisms by which RP5-833A20.1 regulates the expression of NFIA in glioma were investigated. The expression levels of RP5-833A20.1 and NFIA were determined in U251 cells and clinical samples using reverse transcription-quantitative polymerase chain reaction (PCR) analysis. The effects of RP5-833A20.1 on cell proliferation, invasion, cell cycle and apoptosis were evaluated using in vitro assays. The potential changes in protein expression were investigated using western blot analysis. The methylation status of the CpG island in the NFIA promoter was determined using bisulfite PCR (BSP) sequencing. It was found that the expression of RP5-833A20.1 was downregulated, whereas the expression of NFIA was upregulated in glioma tissues, compared with corresponding adjacent nontumor tissues from 20 patients with glioma. The overexpression of RP5-833A20.1 inhibited proliferation and cell cycle progression, and induced apoptosis in the U251 cells. The mRNA and protein levels of NFIA were markedly inhibited by overexpression of RP5-833A20.1 in the U251 cells. The overexpression of RP5-833A20.1 increased the expression of microRNA-382-5p in the U251 cells. The BSP assay revealed that the overexpression of RP5-833A20.1 enhanced the methylation level of the NFIA promoter. These results demonstrated that RP5-833A20.1 inhibited tumor cell proliferation, induced apoptosis and inhibited cell-cycle progression by suppressing the expression of NFIA in U251 cells. Collectively, these results indicated RP5-833A20.1 as a novel therapeutic target for glioma.

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A long non-coding RNA signature in glioblastoma multiforme predicts survival

Cited by 190 publications

References 55 publications

The long non-coding RNA HOTAIR is upregulated in endometrial carcinoma and correlates with poor prognosis

The long non-coding RNA HOTAIR is upregulated in endometrial carcinoma and correlates with poor prognosis

Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

Long non-coding RNA RP5-833A20.1 inhibits proliferation, metastasis and cell cycle progression by suppressing the expression of NFIA in U251 cells

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