It is increasingly evident that many of the genomic mutations in cancer reside inside regions that do not encode proteins. However, these regions are often transcribed into long noncoding RNAs (lncRNAs). The recent application of next-generation sequencing to a growing number of cancer transcriptomes has indeed revealed thousands of lncRNAs whose aberrant expression is associated with different cancer types. Among the few that have been functionally characterized, several have been linked to malignant transformation. Notably, these lncRNAs have key roles in gene regulation and thus affect various aspects of cellular homeostasis, including proliferation, survival, migration or genomic stability. This review aims to summarize current knowledge of lncRNAs from the cancer perspective. It discusses the strategies that led to the identification of cancer-related lncRNAs and the methodologies and challenges involving the study of these molecules, as well as the imminent applications of these findings to the clinic.

The emerging role of lncRNAs in cancer

In addition to mutations or aberrant expression in the protein-coding genes, mutations and misregulation of noncoding RNAs, in particular long noncoding RNAs (lncRNA), appear to play major roles in cancer. Genome-wide association studies of tumor samples have identified a large number of lncRNAs associated with various types of cancer. Alterations in lncRNA expression and their mutations promote tumorigenesis and metastasis. LncRNAs may exhibit tumor-suppressive and -promoting (oncogenic) functions. Because of their genome-wide expression patterns in a variety of tissues and their tissue-specific expression characteristics, lncRNAs hold strong promise as novel biomarkers and therapeutic targets for cancer. In this article, we have reviewed the emerging functions and association of lncRNAs in different types of cancer and discussed their potential implications in cancer diagnosis and therapy. Cancer Res; 77(15); 3965-81. ©2017 AACR.

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Long Noncoding RNA and Cancer: A New Paradigm.

The discovery of numerous non-coding RNA (ncRNA) transcripts in species from yeast to mammals has dramatically altered our understanding of cell biology, especially disease biology such as cancer. In humans, the identification of abundant long ncRNA (lncRNAs) >200 bp in length has catalyzed their characterization as critical components of cancer biology. Recently, roles for lncRNAs as drivers of tumor suppressive and oncogenic functions have appeared in prevalent cancer types, such as breast and prostate cancer. In this review, we will highlight the emerging impact of ncRNAs in cancer research, with a particular focus on the mechanisms and functions of lncRNAs.

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The emergence of lncRNAs in cancer biology.

Long non-coding RNAs (lncRNAs) are emerging as new players in the cancer paradigm demonstrating potential roles in both oncogenic and tumor suppressive pathways. These novel genes are frequently aberrantly expressed in a variety of human cancers, however the biological functions of the vast majority remain unknown. Recently, evidence has begun to accumulate describing the molecular mechanisms by which these RNA species function, providing insight into the functional roles they may play in tumorigenesis. In this review, we highlight the emerging functional role of lncRNAs in human cancer.

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The functional role of long non-coding RNA in human carcinomas

Translation of CircRNAs

Background
Mutations and epigenetic aberrant signaling of growth factors pathways contribute to carcinogenesis. Recent studies reveal that non-coding RNAs are controllers of gene expression. H19 is an imprinted gene that demonstrates maternal monoallelic expression without a protein product; although its expression is shut off in most tissues postnatally, it is re-activated during adult tissue regeneration and tumorigenesis. Moreover, H19 is highly expressed in liver metastasis derived from a range of carcinomas. The objective of this study is to explore the role of H19 in carcinogenesis, and to determine its identification as an anti-tumor target.

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The H19 non-coding RNA is essential for human tumor growth.

Oncofetal H19 RNA promotes tumor metastasis

The oncofetal H19 RNA connection: Hypoxia, p53 and cancer

PDF Signaling Is an Integral Part of the Drosophila Circadian Molecular Oscillator

Most organisms use 24-hr circadian clocks to keep temporal order and anticipate daily environmental changes In Drosophila melanogaster CLOCK (CLK) and CYCLE (CYC) initiates the circadian system by promoting rhythmic transcription of hundreds of genes However, it is still not clear whether high amplitude transcriptional oscillations are essential for circadian timekeeping In order to address this issue, we generated flies in which the amplitude of CLK-driven transcription can be reduced partially (approx 60%) or strongly (90%) without affecting the average levels of CLK-target genes The impaired transcriptional oscillations lead to low amplitude protein oscillations that were not sufficient to drive outputs of peripheral oscillators However, circadian rhythms in locomotor activity were resistant to partial reduction in transcriptional and protein oscillations We found that the resilience of the brain oscillator is depending on the neuronal communication among circadian neurons in the brain Indeed, the capacity of the brain oscillator to overcome low amplitude transcriptional oscillations depends on the action of the neuropeptide PDF and on the pdf-expressing cells having equal or higher amplitude of molecular rhythms than the rest of the circadian neuronal groups in the fly brain Therefore, our work reveals the importance of high amplitude transcriptional oscillations for cell-autonomous circadian timekeeping Moreover, we demonstrate that the circadian neuronal network is an essential buffering system that protects against changes in circadian transcription in the brain

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Shaul Mezan

Papers

The H19 non-coding RNA is essential for human tumor growth.

Oncofetal H19 RNA promotes tumor metastasis

The oncofetal H19 RNA connection: Hypoxia, p53 and cancer

PDF Signaling Is an Integral Part of the Drosophila Circadian Molecular Oscillator

Synergistic Interactions between the Molecular and Neuronal Circadian Networks Drive Robust Behavioral Circadian Rhythms in Drosophila melanogaster