Long non-coding RNAs (lncRNAs, pseudogenes and circRNAs) have recently come into light as powerful players in cancer pathogenesis and it is becoming increasingly clear that they have the potential of greatly contributing to the spread and success of personalized cancer medicine. In this concise review, the authors briefly introduce these three classes of long non-coding RNAs. We then discuss their applications as diagnostic and prognostic biomarkers. Finally, we describe their appeal as targets and as drugs, while pointing out the limitations that still lie ahead of their definitive entry into clinical practice.
- Vitiello M, Tuccoli A, Poliseno L. (2014) Long non-coding RNAs in cancer: implications for personalized therapy. Cell Oncol (Dordr). [Epub ahead of print]. [abstract]
Long non-coding RNAs (lncRNAs) are emerging as important regulators of gene expression; however, in contrast to transcription factors, their functional domain architecture remains poorly understood. Now, a new method has been developed to simultaneously map RNA–RNA, RNA–DNA and RNA–protein interactions at the level of individual RNA domains with increased sensitivity.
Quinn et al. developed a method called domain-specific chromatin isolation by RNA purification (dChIRP), in which several antisense oligonucleotide pools are used to target specific domains of lncRNAs. In this method, cells are subjected to fixation, crosslinking and sonication, and the resultant sheared chromatin is hybridized to the biotinylated oligonucleotide pools to recover chromatin fragments containing specific lncRNA domains of interest. The RNA, DNA and protein components associated with the lncRNA domains can then be analysed separately.
from ScienceNetwork WA by Anika Rodgers
AUSTRALIAN researchers have uncovered new targets for therapy in the childhood cancer neuroblastoma.
Histone Modification Group and Children’s Cancer Institute Australia for Medical Research’s Tao Liu says the researchers have been studying neuroblastoma in the hope of developing novel treatments.
“Neuroblastoma is the most common solid tumour in early childhood and it accounts for 15 per cent of all childhood cancer death,” Dr Liu says.
“In Australia, cancer is the most common cause of death from disease for children, and neuroblastoma is one of the most devastating types,” Dr Liu says.
Neuroblastoma affects the peripheral nervous system in children, and in most cases presents in the adrenal glands, found above the kidneys.
from Bioresearch Online by C. Rajan, contributing writer
Researchers at the Indiana University School of Medicine have just discovered a molecule which allows the heart to block a protein that creates genetic disruptions when the heart is subjected to stressful conditions, such as high blood pressure. This previously unknown molecule could help in treating and preventing heart failure.
The newly discovered molecule is a long non-coding RNA (lncRNA), which the researchers have named Myheart—for myosin heavy-chain-associated RNA transcript. Until now, the role of long non-coding RNA in the heart has been unknown.
Dr. Ching-Pin Chang, M.D., Ph.D., associate professor of medicine at the Indiana University School of Medicine, led the research team, which found that insufficient levels of this new molecule, Myheart, could lead to heart failure. When they restored levels of Myheart in mice experiencing heart failure, the progression to heart failure ceased.
The transcription factor SOX2 is essential for maintaining pluripotency in a variety of stem cells. It has important functions during embryonic development, is involved in cancer stem cell maintenance, and is often deregulated in cancer. The mechanism of SOX2 regulation has yet to be clarified, but the SOX2 gene lies in an intron of a long multi-exon non-coding RNA called SOX2 overlapping transcript (SOX2OT).
Here, researchers from the University of Auckland show that the expression of SOX2 and SOX2OT is concordant in breast cancer, differentially expressed in estrogen receptor positive and negative breast cancer samples and that both are up-regulated in suspension culture conditions that favor growth of stem cell phenotypes. Importantly, ectopic expression of SOX2OT led to an almost 20-fold increase in SOX2 expression, together with a reduced proliferation and increased breast cancer cell anchorage-independent growth. We propose that SOX2OT plays a key role in the induction and/or maintenance of SOX2 expression in breast cancer.
- Askarian-Amiri ME, Seyfoddin V, Smart CE, Wang J, Kim JE, et al. (2014) Emerging Role of Long Non-Coding RNA SOX2OT in SOX2 Regulation in Breast Cancer. PLoS ONE 9(7): e102140. [article]