ABSTRACT
Multifactorial diseases such as cancer, cardiovascular conditions and neurological, immunological and metabolic disorders are a group of diseases caused by the combination of genetic and environmental factors. High-throughput RNA sequencing (RNA-seq) technologies have revealed that less than 2% of the genome corresponds to protein-coding genes, although most of the human genome is transcribed. The other transcripts include a large variety of non-coding RNAs (ncRNAs), and the continuous generation of RNA-seq data shows that ncRNAs are strongly deregulated and may be important players in pathological processes. A specific class of ncRNAs, the long non-coding RNAs (lncRNAs), has been intensively studied in human diseases. For clinical purposes, lncRNAs may have advantages mainly because of their specificity and differential expression patterns, as well as their ideal qualities for diagnosis and therapeutics. Multifactorial diseases are the major cause of death worldwide and many aspects of their development are not fully understood. Recent data about lncRNAs has improved our knowledge and helped risk assessment and prognosis of these pathologies. This review summarizes the involvement of some lncRNAs in the most common multifactorial diseases, with a focus on those with published functional data.
ABSTRACT
In breast cancer, lymph node (LN) metastasis is one of the strongest prognostic factors at diagnosis. Therefore the identification of molecular markers with metastatic potential that promote the development of LN metastasis is of critical clinical relevance. In this study, we evaluated the copy number status of the FOSL1, GSTP1, NTSR1, FADD and CCND1 genes by TaqMan assays in 137 breast cancer patients, 84 with LN metastasis (LN+) and 53 with no LN metastasis (LN-). The copy number data for four of these genes (FOSL1, GSTP1, FADD and CCND1) were integrated with their mRNA expression levels in 31 patients. In both groups of patients, gains were the most frequent copy number alteration (CNA) observed, involving mainly the CCND1, NTSR1 and FADD genes; mRNA overexpression was more commonly observed for the CCND1 and FADD genes. For the FADD gene in the LN+ group, gene expression was shown to be dependent on CNAs; for the other genes no association was found. In conclusion, increase copy number and mRNA overexpression of FOSL1, GSTP1, FADD, NTSR1 and CCND1 genes are frequently observed in primary breast tumors, and except for the FADD gene, they occur independently and irrespectively of the patients' LN axillary metastatic status.