Aberrant Expression of Long Noncoding RNAs in Cervical Intraepithelial Neoplasia

Gibb, Ewan A.; Becker‐Santos, Daiana D.; Enfield, Katey S.S.; Guillaud, Martial; Niekerk, Dirk van; Matisic, Jasenka; MacAulay, Calum; Lam, Wan L.

doi:10.1097/igc.0b013e318272f2c9

Cited by 28 publications

(24 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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

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

Section: Lncrnas In Cancermentioning

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

show abstract

“…It is increasingly understood that lncRNAs are important molecules involved not only in normal development but also in tumorigenesis [7]. In fact, there are emerging evidence showing that lncRNAs are involved in pathological development of cervical cancer [8]. For example, MEG3 (maternally expressed 3) is a lncRNA playing tumor suppressor role in several cancers by inducing cell cycle arrest and apoptosis [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA MALAT1 modulates radiosensitivity of HR-HPV+ cervical cancer via sponging miR-145

He²,

et al. 2015

View full text Add to dashboard Cite

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a lncRNA playing oncogenic role in several cancers, including cervical cancer. However, its role in radiosensitivity of cervical cancer is not yet well understood. This study explored the role of MALAT1 in radiosensitivity of high-risk human papillomavirus (HR-HPV)-positive cervical cancer and whether there is a ceRNA mechanism which participated in its regulation over radiosensitivity. Based on tissue samples from 50 cervical cancer cases and 25 healthy controls, we found MALAT1 expression was significantly higher in radioresistant than in radiosensitive cancer cases. In addition, MALAT1 and miR-145 expression inversely changed in response to irradiation in HR-HPV+ cervical cancer cells. By using clonogenic assay and flow cytometry analysis of cell cycle distribution and apoptosis, we found CaSki and Hela cells with knockdown of MALAT1 had significantly lower colony formation, higher ratio of G2/M phase block and higher ratio of cell apoptosis. By performing RNA-binding protein immunoprecipitation (RIP) assay and RNA pull-down assay, we confirmed that miR-145 and MALAT1 were in the same Ago2 complex and there was a reciprocal repression between them. Then, we explored the function of MALAT1-miR-145 in radiosensitivity of cervical cancers cells and demonstrated that si-MALAT1 and miR-145 had some level of synergic effect in reducing cancer cell colony formation, cell cycle regulation, and inducing apoptosis. These findings provide an important clue about microRNA-lncRNA interaction in the mechanism of radioresistance of cervical cancer.

show abstract

“…However, studies on the role of lncRNAs in CC are very preliminary. Until now only one research has detected increased levels of aberrant lncRNA expression in cervical intraepithelial neoplasia (CIN) specimens representing mild, moderate, and severe histopathologic grades, respectively, suggesting that lncRNAs may play important roles in the development and progression of precancerous lesions or carcinomas [10]. However, the overall pathophysiological contributions of lncRNAs in CC remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Long Noncoding RNA-EBIC Promotes Tumor Cell Invasion by Binding to EZH2 and Repressing E-Cadherin in Cervical Cancer

et al. 2014

View full text Add to dashboard Cite

In recent years, long noncoding RNAs (lncRNAs) have been demonstrated to play key roles in tumorgenesis. However, the contributions of lncRNAs to cervical cancer (CC) remain largely unknown. In this study, differentially expressed lncRNAs and mRNAs in cervical cancer and paired peritumoral tissues were detected by transcriptome microarray analysis. We found 708 probe sets of lncRNAs increased and 836 probe sets decreased in CC tissues, while 1288 mRNA differential probe sets increased and 901 mRNA probe sets decreased. The results were validated by quantitative real-time polymerase chain reaction (qPCR). Then, we found a specific differentially expressed lncRNA can physically bind to enhancer of zeste homolog2 (EZH2) by using RNA immunoprecipitation. We termed it as EZH2-binding lncRNA in cervical cancer [lncRNA-EBIC]. Wound healing assays and Matrigel invasion assays were used to determine the function of this lncRNA by silencing it. We observed that the migration and invasion of cervical cancer cells in vitro were inhibited upon suppression of lncRNA-EBIC by siRNA. We also found that the association between lncRNA-EBIC and EZH2 was required for the repression of E-cadherin, which was a key molecular in the metastasis of cervical cancer.ConclusionThese results demonstrated that lncRNA-EBIC was an oncogenic lncRNA, which could promote tumor cell invasion in CC by binding to EZH2 and inhibiting E-cadherin expression.

show abstract

Aberrant Expression of Long Noncoding RNAs in Cervical Intraepithelial Neoplasia

Abstract: Through the analysis of L-SAGE libraries constructed from cervical specimens, we provide the first lncRNA expression profile of the cervix and demonstrate aberrant expression in early-stage neoplasia.

Cited by 28 publications

References 29 publications

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

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

Long non-coding RNA MALAT1 modulates radiosensitivity of HR-HPV+ cervical cancer via sponging miR-145

Long Noncoding RNA-EBIC Promotes Tumor Cell Invasion by Binding to EZH2 and Repressing E-Cadherin in Cervical Cancer

Contact Info

Product

Resources

About