Search Results for: long noncoding rna expression

LncRNA: A link between RNA and cancer

Unraveling the gene expression networks governing cancer initiation and development is essential while remains largely uncompleted. With the innovations in RNA-seq technologies and computational biology, long noncoding RNAs (lncRNAs) are being identified and characterized at a rapid pace. Recent findings reveal that lncRNAs are implicated in serial steps of cancer development. These lncRNAs interact with DNA, RNA, protein molecules and/or their combinations, acting as an essential regulator in chromatin organization, transcriptional and post-transcriptional regulation. Their misexpression confers the cancer cell capacities for tumor initiation, growth, and metastasis. The review here will emphasize their aberrant expression and function in cancer, and the roles in cancer diagnosis and therapy will be also discussed.

lncRNA

  • Yanga G, Lub X, Yuanc L. (2014) LncRNA: A link between RNA and cancer. Biochimica et Biophysica Acta (BBA) – Gene Regulatory Mechanisms [Epub ahead of print]. [abstract]

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Genome-wide Mapping and Characterization of Notch-Regulated Long Noncoding RNAs

Notch signaling is a key developmental pathway that is subject to frequent genetic and epigenetic perturbations in many different human tumors.

Here a team led by researchers from the NYU School of Medicine investigate whether long noncoding RNA (lncRNA) genes, in addition to mRNAs, are key downstream targets of oncogenic Notch1 in human T cell acute lymphoblastic leukemia (T-ALL). By integrating transcriptome profiles with chromatin state maps, they have uncovered many previously unreported T-ALL-specific lncRNA genes, a fraction of which are directly controlled by the Notch1/Rpbjκ activator complex. Finally they have shown that one specific Notch-regulated lncRNA, LUNAR1, is required for efficient T-ALL growth in vitro and in vivo due to its ability to enhance IGF1R mRNA expression and sustain IGF1 signaling. These results confirm that lncRNAs are important downstream targets of the Notch signaling pathway, and additionally they are key regulators of the oncogenic state in T-ALL.

lncRNA

  • Trimarchi T, Bilal E, Ntziachristos P, Fabbri G, Dalla-Favera R, Tsirigos A, Aifantis I. (2014) Genome-wide Mapping and Characterization of Notch-Regulated Long Noncoding RNAs in Acute Leukemia. Cell 158(3):593-606. [abstract]

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Epigenetic coordination of embryonic heart transcription by dynamically regulated long noncoding RNAs

lncRNA

The role of noncoding RNAs in mammalian biology is of great interest, especially since the Encyclopedia of DNA Elements results were published. Many have studied microRNAs in the heart, but little is known about their larger cousins, long noncoding RNAs (lncRNAs). Here, researchers from the Washington University School of Medicine used genome-wide sequencing and improved bioinformatics to quantify lncRNA expression in mouse hearts, define a subset of cardiac-specific lncRNAs, and measure dynamic lncRNA regulation during the transition between embryo and adult, and in the adult heart after experimental pressure overload (a model resembling human hypertensive cardiomyopathy). They linked specific regulated lncRNAs to cardiac-expressed mRNAs that they target and, through network analyses, discovered a broader role of regulated cardiac lncRNAs as modulators of key cardiac transcriptional pathways.

  • Matkovich SJ, Edwards JR, Grossenheider TC, de Guzman Strong C, Dorn GW 2nd. (2014) Epigenetic coordination of embryonic heart transcription by dynamically regulated long noncoding RNAs. Proc Natl Acad Sci U S A 111(33):12264-9. [abstract]

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Long Noncoding RNA Regulating Apoptosis Discovered

from Genetic Engineering News

Scientists from the University of São Paulo (USP) have identified an RNA molecule known as INXS that, although containing no instructions for the production of a protein, modulates the action of an important gene that impacts apoptosis.

According to Sergio Verjovski-Almeida, Ph.D., professor at the USP Chemistry Institute, INXS expression is generally diminished in cancer cells, and methods that are capable of stimulating the production of this noncoding RNA can be used to treat tumors. In experiments on mice, the USP scientists were able to effect a 10-fold reduction in the volume of subcutaneous malignant tumors by administering local injections of a plasmid containing INXS.

The team’s findings (“Long noncoding RNA INXS is a critical mediator of BCL-XS induced apoptosis”) were published in Nucleic Acids Research.

The group headed by Dr. Verjovski-Almeida at USP has been investigating the regulatory role of so-called intronic nonprotein-coding genes—those found in the same region of the genome as a coding gene but on the opposite DNA strand. INXS, for example, is an RNA expressed on the opposite strand of a gene coding for  the BCL-X protein.

“We were studying several protein-coding genes involved in cell death in search of evidence that one of them was regulated by intronic noncoding RNA. That was when we found the gene for BCL-X, which is located on chromosome 20,” he explained.

(read more…)

 

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Gastric juice long noncoding RNA used as a tumor marker for screening gastric cancer

Long noncoding RNAs (lncRNAs) play a crucial role in tumorigenesis. However, the value of lncRNAs in the diagnosis of gastric cancer remains unknown. To identify whether lncRNA-AA174084 is a potential marker for the early diagnosis of gastric cancer (GC), the authors investigated its levels in tissues, blood, and gastric juices from patients with various stage of gastric tumorigenesis.

Total RNA in 860 specimens from patients and healthy controls was extracted. Levels of AA174084 in 134 paired GC tissues, 127 gastric mucosal tissues, 335 plasma samples, and 130 gastric juice samples at each stage of gastric tumorigenesis were measured using real-time reverse transcriptase-polymerase chain reaction analysis. The potential association between AA174084 levels and patients’ clinicopathologic features were analyzed. A receiver operating characteristic (ROC) curve was constructed for differentiating GC patients from controls.

lncRNAExpression levels of AA174084 were down-regulated significantly in 95 of 134 GC tissues (71%) compared with the levels in paired, adjacent, normal tissues (P < .001). AA174084 levels had significant, negative correlations with age (P = .031), Borrmann type (P = .016), and perineural invasion (P = .032). Plasma AA174084 levels in patients with GC dropped markedly on day 15 after surgery compared with preoperative levels (P < .001) and were associated with invasion (P = .049) and lymphatic metastasis (P = .042). AA174084 levels in gastric juice from patients with GC were significantly higher than the levels in normal mucosa or in patients with minimal gastritis, gastric ulcers, and atrophic gastritis (P < .001). The area under ROC was up to 0.848 (P < .001).

The authors conclude that AA174084 may have potential as marker for the early diagnosis of GC.

  • Shao Y, Ye M, Jiang X, Sun W, Ding X, Liu Z, Ye G, Zhang X, Xiao B, Guo J. (2014) Gastric juice long noncoding RNA used as a tumor marker for screening gastric cancer. Cancer [Epub ahead of print]. [abstract]

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