An Insertion/Deletion Polymorphism within RERT-lncRNA Modulates Hepatocellular Carcinoma Risk

Zhu, Zhansheng; Gao, Xueren; He, Yan; Zhao, Hua; Yu, Qiang; Jiang, Deke; Zhang, Pingzhao; Ma, Xiaopin; Huang, Huaxiong; Dong, Dong; Wan, Jieqing; Gu, Zhenyong; Jiang, Xinghong; Liu, Yu; Gao, Yuzhen

doi:10.1158/0008-5472.can-12-0010

Cited by 88 publications

(69 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, affecting apoptosis by DNMT, ABCG2 and TSA also PRKACB, CREB and MLL has been identified in HCC [25,35,[39][40][41][42][43][44][45][46][47][48][49][50][51]. In addition, there is evidence that lncRNAs have important roles in promoting metastasis by targeting factors such as HOXD, VEGF, MMP-9, PRC2, H3K27, RBM38, caspase-3/-8, Bax, Bcl-2, BclxL, ZEB, and IL-11 [23,33,[52][53][54][55][56]. Moreover, lncRNA can inhibit angiogenesis by targeting PGK1 [13,57].…”

Section: Functions and Pathways Involving Lncrnas Targetsmentioning

confidence: 99%

Progress and Prospects of Long Noncoding RNAs (lncRNAs) in Hepatocellular Carcinoma

Li¹,

Chen²,

Zhang³

et al. 2015

Cell Physiol Biochem

171

141

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is one of the most frequently occurring cancers with poor prognosis, and novel diagnostic or prognostic biomarkers and therapeutic targets for HCC are urgently required. With the advance of high-resolution microarrays and massively parallel sequencing technology, lncRNAs are suggested to play critical roles in the tumorigenesis and development of human HCC. To date, dysregulation of many HCC-related lncRNAs such as HULC, HOTAIR, MALAT1, and H19 have been identified. From transcriptional “noise” to indispensable elements, lncRNAs may re-write the central dogma. Also, lncRNAs found in body fluids have demonstrated their utility as fluid-based noninvasive markers for clinical use and as therapeutic targets for HCC. Even though several lncRNAs have been characterized, the underlying mechanisms of their contribution to HCC remain unknown, and many important questions about lncRNAs need resolving. A better understanding of the molecular mechanism in HCC-related lncRNAs will provide a rationale for novel effective lncRNA-based targeted therapies. In this review, we highlight the emerging roles of lncRNAs in HCC, and discuss their potential clinical applications as biomarkers for the diagnosis, prognosis, monitoring and treatment of HCC.

show abstract

Section: Functions and Pathways Involving Lncrnas Targetsmentioning

confidence: 99%

Progress and Prospects of Long Noncoding RNAs (lncRNAs) in Hepatocellular Carcinoma

Li¹,

Chen²,

Zhang³

et al. 2015

Cell Physiol Biochem

171

141

View full text Add to dashboard Cite

show abstract

“…71 The G allele of rs6983267, in addition to being related to a significantly increased risk of CRC, 72 results in more CCAT2 transcripts than the T allele, which further affects the regulation of MYC by CCAT2; thus different rs6983267 alleles can affect CCAT2 expression and function. 58 Studies examining other cancer types have shown that SNPs in the key regulatory regions of an lncRNA can alter its structural motifs 73 and may consequently affect its expression and function in malignancies, 74 additionally contributing to cancer risk. 75,76 SNPs in the cancer-associated lncRNAs could potentially have pivotal roles in colorectal tumorigenesis and progression.…”

Section: Regulation Of Lncrna Expressionmentioning

confidence: 99%

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

Pan

2014

Modern Pathology

102

View full text Add to dashboard Cite

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 ...

show abstract

“…GTP-binding protein 4b and EGLN2) (34). Subsequently, they proved using the Open Reading Frame (ORF) Finder and codon substitution frequency analysis that the overexpressed lncRNA, MVIH, in hepatocellular carcinoma (HCC) is a noncoding RNA transcribed independently of the RPS24 gene and that no correlation existed between the transcriptional levels of RPS24 and MVIH (33).…”

mentioning

confidence: 99%

Differential expression of long non-coding RNAs in bleomycin-induced lung fibrosis

Cao

Zhang

Wang

et al. 2013

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Abstract. Recent studies suggest that long non-coding RNAs (lncRNAs) are more involved in human diseases than previously realized. A growing body of evidence links lncRNA mutation and dysregulation to diverse human diseases. However, the association of lncRNAs with the pathogenesis of lung fibrosis remains poorly understood. In this study, we detected changes in hydroxyproline and collagen levels, as well as the ultrastructure of lung tissue to develop a rat model of lung fibrosis. The differentially expressed lncRNAs and mRNA profiles between fibrotic lung and normal lung tissue were analyzed using microarrays. Gene Ontology analysis and pathway analysis were performed for further research. Two differentially expressed lncRNAs, namely, AJ005396 and S69206, were detected by in situ hybridization to validate the microarray data. The results revealed that the number of collagen fibers in the interstitial lung tissue significantly increased in the model group compared with the normal group. In total, 210 and 358 lncRNAs were upregulated and downregulated, respectively, along with 415 upregulated and 530 downregulated mRNAs in the rats with lung fibrosis. AJ005396 and S69206 were upregulated in the fibrotic lung tissue, consistent with the microarray data, and were located in the cytoplasm of the interstitial lung cells. In conclusion, the expression profile of the lncRNAs was significantly altered in the fibrotic lung tissue and these transcripts are potential molecular targets for inhibiting the development of lung fibrosis. IntroductionIdiopathic pulmonary fibrosis (IPF) is a common, chronic, progressive and usually lethal fibrotic lung disease with poor prognosis (1). This disease is characterized by focal areas of alveolar epithelial cell injury and the excessive proliferation of mesenchymal cells in the interstitium, which results in the excessive deposition of extracellular matrix (ECM) and distorted architecture leading to impaired gas exchange (2,3). Although many pathobiological concepts are emerging, including the role of aging and cellular senescence, oxidative stress, endoplasmic reticulum stress, cellular plasticity, microRNA (miRNA) and mechanotransduction, the molecular mechanisms behind IPF are not yet completely understood (4).The Encyclopedia of DNA Elements (ENCODE) project, which aimed to comprehensively characterize the human genome, has shown that >90% of the genome has been transcribed; however, only 1-2% of that is composed of genes (5). The majority of these transcripts are not translated into proteins and are, therefore, termed non-coding RNAs (ncRNAs).Long non-coding RNAs (lncRNAs), a type of ncRNA, vary in size from 200 bp to >100 kb, and are transcribed by RNA polymerase II (6). They play an important role in imprinting (7), enhancing various biological functions (8), X chromosome inactivation (9), chromatin structure (10) and genomic rearrangement during the generation of antibody diversity (11). Thus, lncRNAs are critical for normal development and, in many cases, are deregulated in d...

show abstract

An Insertion/Deletion Polymorphism within RERT-lncRNA Modulates Hepatocellular Carcinoma Risk

Cited by 88 publications

References 40 publications

Progress and Prospects of Long Noncoding RNAs (lncRNAs) in Hepatocellular Carcinoma

Progress and Prospects of Long Noncoding RNAs (lncRNAs) in Hepatocellular Carcinoma

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

Differential expression of long non-coding RNAs in bleomycin-induced lung fibrosis

Contact Info

Product

Resources

About