Non-coding RNAs In Cancer Research Articles

A novel reannotation strategy for dissecting DNA methylation patterns of human long intergenic non-coding RNAs in cancers.

Despite growing consensus that long intergenic non-coding ribonucleic acids (lincRNAs) are modulators of cancer, the knowledge about the deoxyribonucleic acid (DNA) methylation patterns of lincRNAs in cancers remains limited. In this study, we constructed DNA methylation profiles for 4629 tumors and 705 normal tissue samples from 20 different types of human cancer by reannotating data of DNA methylation arrays. We found that lincRNAs had different promoter methylation patterns in cancers. We classified 2461 lincRNAs into two categories and three subcategories, according to their promoter methylation patterns in tumors. LincRNAs with resistant methylation patterns in tumors had conserved transcriptional regulation regions and were ubiquitously expressed across normal tissues. By integrating cancer subtype data and patient clinical information, we identified lincRNAs with promoter methylation patterns that were associated with cancer status, subtype or prognosis for several cancers. Network analysis of aberrantly methylated lincRNAs in cancers showed that lincRNAs with aberrant methylation patterns might be involved in cancer development and progression. The methylated and demethylated lincRNAs identified in this study provide novel insights for developing cancer biomarkers and potential therapeutic targets.

Noncoding RNAs in cancer and cancer stem cells

In recent years, it has become increasingly apparent that noncoding RNAs (ncRNA) are of crucial importance for human cancer. The functional relevance of ncRNAs is particularly evident for microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). miRNAs are endogenously expressed small RNA sequences that act as post-transcriptional regulators of gene expression and have been extensively studied for their roles in cancers, whereas lncRNAs are emerging as important players in the cancer paradigm in recent years. These noncoding genes are often aberrantly expressed in a variety of human cancers. However, the biological functions of most ncRNAs remain largely unknown. Recently, evidence has begun to accumulate describing how ncRNAs are dysregulated in cancer and cancer stem cells, a subset of cancer cells harboring self-renewal and differentiation capacities. These studies provide insight into the functional roles that ncRNAs play in tumor initiation, progression, and resistance to therapies, and they suggest ncRNAs as attractive therapeutic targets and potentially useful diagnostic tools.

Long non-coding RNAs in cancer

Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, the Third Xiangya Hospital, Central South University, Changsha 410013, China; Key Laboratory of Carcinogenesis of Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha 410078, China; Department of Stomatology, the Second Xiangya Hospital, Central South University, Changsha 410011, China; Department of Stomatology, Xiangya Hospital, Central South University, Changsha 410008, China; Key Laboratory of Information System Engineering, National University of Defense Technology, Changsha 410073, China; Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, School of Medicine, University of Louisville, Louisville, KY 40202, USA

Specific small nucleolar RNA expression profiles in acute leukemia

Apart from microRNAs, little is known about the regulation of expression of non-coding RNAs in cancer. We investigated whether small nucleolar RNAs (snoRNAs) accumulation displayed specific signatures in acute myeloblastic and acute lymphoblastic leukemias. Using microarrays and high-throughput quantitative PCR (qPCR), we demonstrate here that snoRNA expression patterns are negatively altered in leukemic cells compared with controls. Interestingly, a specific signature was found in acute promyelocytic leukemia (APL) with ectopic expression of SNORD112-114 snoRNAs located at the DLK1-DIO3 locus. In vitro experiments carried out on APL blasts demonstrate that transcription of these snoRNAs was lost under all-trans retinoic acid-mediated differentiation and induced by enforced expression of the PML-RARalpha fusion protein in negative leukemic cell lines. Further experiments revealed that the SNORD114-1 (14q(II-1)) variant promoted cell growth through cell cycle modulation; its expression was implicated in the G0/G1 to S phase transition mediated by the Rb/p16 pathways. This study thus reports three important observations: (1) snoRNA regulation is different in normal cells compared with cancer cells; (2) a relationship exists between a chromosomal translocation and expression of snoRNA loci; and (3) snoRNA expression can affect Rb/p16 cell cycle regulation. Taken together, these data strongly suggest that snoRNAs have a role in cancer development.

Emerging links between epigenetic alterations and dysregulation of noncoding RNAs in cancer

Epigenetic changes, including DNA methylation and histone modification, play key roles in the dysregulation of tumor-related genes, thereby affecting numerous cellular processes, including cell proliferation, cell adhesion, apoptosis, and metastasis. In recent years, numerous studies have shown that noncoding RNAs (ncRNAs) are key players in the initiation and progression of cancer and epigenetic mechanisms are deeply involved in their dysregulation. Indeed, the growing list of microRNA (miRNA) genes aberrantly methylated in cancer suggests that a large number of miRNAs exert tumor-suppressive or oncogenic effects. In addition, it now appears that long ncRNAs may be causally related to epigenetic dysregulation of critical genes in cancer. Dissection of the relationships between ncRNAs and epigenetic alterations may lead to the development of novel approaches to the diagnosis and treatment of cancer.

Emerging Roles for Long Non-Coding RNAs in Cancer and Neurological Disorders.

The recent discovery of thousands of long non-coding (lnc)RNAs in the human genome has prompted investigation of the potential roles of these molecules in human biology and medicine. Indeed, it is now well documented that many lncRNAs are involved in key biological processes, including dosage compensation, genomic imprinting, chromatin regulation, alternative splicing of pre-mRNA, nuclear organization; and potentially many other biological processes, which are yet to be elucidated. Recently, a number of studies have also reported that lncRNAs are dysregulated in a number of human diseases, including several cancers and neurological disorders. Although many of these studies have fallen short of implicating lncRNAs as causative, they suggest potential roles that warrant further in depth investigations. In this review, we discuss the current state of knowledge regarding the roles of lncRNAs in cancer and neurological disorders, and suggest potential future directions in this rapidly emerging field.

Keystone Symposia 40th Season: MicroRNAs and Noncoding RNAs in Cancer

This year's 40th season of Keystone symposia meetings was held in Banff, Alberta, Canada, on February 11-16 and sponsored by Astellas Pharma and Regulus Therapeutics. The meeting was organized by Gregory Hannon, Curtis Harris, and Martine Roussel and centered on microRNAs (miRNA), noncoding RNAs, and cancer. The meeting was grouped around the following topical areas: miRNA mechanisms, oncogenesis, immune response, angiogenesis and metastasis, cancer biomarkers, stem cells, and therapeutics. This report highlights findings and concepts presented during this meeting.

MiR signatures and the role of miRs in acute myeloid leukaemia

Acute myeloid leukaemia (AML) is a hematopoietic stem cell disorder in which neoplastic myeloblasts are arrested in an immature stage of differentiation. Recent publications have underlined the involvement of non-coding RNAs in cancer and particularly in AML development, with several studies regarding their possible contribution to the evolution of the disease. MicroRNAs (miRs) are a class of single-stranded non-coding RNAs that bind to the 3′-untranslated region of target mRNAs and thus negatively regulate gene expression, by translation repression or mRNA degradation. Abnormal expression of miRs in AML has been described and we here review the current data from miR expression profiles. Additionally, we review the current knowledge on the biological function of individual miRs in the development of AML.