Transcriptional profiling of long non-coding RNAs and novel transcribed regions across a diverse panel of archived human cancers

Brunner, Alayne; Beck, Andrew H.; Edris, Badreddin; Sweeney, Robert T.; Zhu, Shirley; Li, Rui; Montgomery, Kelli; Varma, Sushama; Gilks, Thea; Guo, Xiangqian; Foley, Joseph W.; Witten, Daniela; Giacomini, Craig P.; Flynn, Ryan A.; Pollack, Jonathan R.; Tibshirani, Robert; Chang, Howard Y.; Rijn, Matt van de; West, Robert B.

doi:10.1186/gb-2012-13-8-r75

Cited by 224 publications

(174 citation statements)

References 28 publications

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“…51 In our study, a number of the top hits across multiple sarcoma subtypes were lncRNAs, including D21S2088E in angiosarcoma and PCGEM1 in Ewing's sarcoma, both of which were the most significantly upregulated transcripts relative to all of our other samples. PCGEM1 is normally expressed only in prostate tissue; significant upregulation of PCGEM1 is an established biomarker for prostate cancer.…”

Section: Therapeutic Targets In Human Soft Tissue Tumors Ae Sarver Et Almentioning

confidence: 61%

Identification, by systematic RNA sequencing, of novel candidate biomarkers and therapeutic targets in human soft tissue tumors

Sarver

Thayanithy

et al. 2015

Laboratory Investigation

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Human sarcomas comprise a heterogeneous group of more than 50 subtypes broadly classified into two groups: bone and soft tissue sarcomas. Such heterogeneity and their relative rarity have made them challenging targets for classification, biomarker identification, and development of improved treatment strategies. In this study, we used RNA sequencing to analyze 35 primary human tissue samples representing 13 different sarcoma subtypes, along with benign schwannoma, and normal bone and muscle tissues. For each sarcoma subtype, we detected unique messenger RNA (mRNA) expression signatures, which we further subjected to bioinformatic functional analysis, upstream regulatory analysis, and microRNA (miRNA) targeting analysis. We found that, for each sarcoma subtype, significantly upregulated genes and their deduced upstream regulators included not only previously implicated known players but also novel candidates not previously reported to be associated with sarcoma. For example, the schwannoma samples were characterized by high expression of not only the known associated proteins GFAP and GAP43 but also the novel player GJB6. Further, when we integrated our expression profiles with miRNA expression data from each sarcoma subtype, we were able to deduce potential key miRNA-gene regulator relationships for each. In the Ewing's sarcoma and fibromatosis samples, two sarcomas where miR-182-5p is significantly downregulated, multiple predicted targets were significantly upregulated, including HMCN1, NKX2-2, SCNN1G, and SOX2. In conclusion, despite the small number of samples per sarcoma subtype, we were able to identify key known players; concurrently, we discovered novel genes that may prove to be important in the molecular classification of sarcomas and in the development of novel treatments.

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Section: Therapeutic Targets In Human Soft Tissue Tumors Ae Sarver Et Almentioning

confidence: 61%

Identification, by systematic RNA sequencing, of novel candidate biomarkers and therapeutic targets in human soft tissue tumors

Sarver

Thayanithy

et al. 2015

Laboratory Investigation

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“…Previous studies have demonstrated that the expression of lncRNAs is dysregulated in a variety of human cancers, and these aberrant lncRNAs may serve key roles during the initiation and progression of cancer (12)(13)(14). However, lncRNA research remains premature when compared to what is understood about protein-coding RNA and microRNA.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of BC200 in ovarian cancer contributes to cancer cell proliferation and chemoresistance to carboplatin

Wang

Ren

et al. 2015

Oncology Letters

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Abstract. Previous studies have demonstrated that long non-coding RNAs (lncRNAs) serve an important role in carcinogenesis. BC200 is a lncRNA that is reportedly associated with ovarian cancer. The aim of the present study was to investigate this potential association between BC200 and ovarian cancer, and to subsequently analyze the biological function of BC200 in the disease. BC200 expression was compared in ovarian cancer tissue and normal ovarian tissue samples through the use of quantitative polymerase chain reaction. To allow the biological function of BC200 in ovarian cancer to be analyzed, small interfering RNA was used to knock down the expression of BC200 in SKOV3 and A2780 ovarian cancer cells. The proliferative, invasive and migratory abilities of the cells were identified by means of cell counting kits and Transwell assays. Carboplatin was also used to treat the ovarian cancer cells, and a luminescent cell viability assay was subsequently used to detect the sensitivity of the cells to the carboplatin. The results demonstrated that BC200 expression was reduced in ovarian cancer compared with normal ovarian tissue samples. In the SKOV3 and A2780 cells, BC200 exerted no effect on invasive or migratory ability, however, the inhibition of BC200 was demonstrated to promote cell proliferation. Additionally, it was observed that carboplatin induced BC200 expression in the cell lines, and that the inhibition of BC200 decreased the sensitivity of the cells to the drug. BC200 is therefore likely to have a tumor suppressive function in ovarian cancer by affecting cell proliferation. Furthermore, BC200 appears to serve a role in the mediation of carboplatin-induced ovarian cancer cell death.

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“…Using a range of techniques, such as microarray, 18 RNA sequencing, 19 and real-time PCR, 20 many studies have confirmed that lncRNA expression levels differ between normal and tumor tissues and vary among tumor types. [21][22][23] Although some of these abnormal expression patterns may be secondary effects from the cancer transformation, several factors suggest that lncRNAs could influence tumorigenesis. These factors include the tremendous complexity and diversity of the lncRNA landscape, the finding that lncRNAs are often located at crucial sites (eg, regions of singlenucleotide polymorphisms (SNPs), amplifications, or at common breakpoints), the presence of sequence motifs and other elements that result in specific structures, their regulation, and their functional relationships with other nucleic acids and proteins.…”

Section: Lncrnas In Cancermentioning

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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Transcriptional profiling of long non-coding RNAs and novel transcribed regions across a diverse panel of archived human cancers

Cited by 224 publications

References 28 publications

Identification, by systematic RNA sequencing, of novel candidate biomarkers and therapeutic targets in human soft tissue tumors

Identification, by systematic RNA sequencing, of novel candidate biomarkers and therapeutic targets in human soft tissue tumors

Downregulation of BC200 in ovarian cancer contributes to cancer cell proliferation and chemoresistance to carboplatin

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

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