Article

A NEW TUMOR SUPPRESSOR GENE CANDIDATE REGULATED BY THE NON-CODING RNA PCA3 IN HUMAN PROSTATE CANCER

UT Graduate School of Biomedical Sciences at Houston: Dissertations and Theses 01/2010;
Source: OAI

ABSTRACT Prostate cancer is the second leading cause of cancer-related death and the most common non-skin cancer in men in the USA. Considerable advancements in the practice of medicine have allowed a significant improvement in the diagnosis and treatment of this disease and, in recent years, both incidence and mortality rates have been slightly declining. However, it is still estimated that 1 man in 6 will be diagnosed with prostate cancer during his lifetime, and 1 man in 35 will die of the disease. In order to identify novel strategies and effective therapeutic approaches in the fight against prostate cancer, it is imperative to improve our understanding of its complex biology since many aspects of prostate cancer initiation and progression still remain elusive. The study of tumor biomarkers, due to their specific altered expression in tumor versus normal tissue, is a valid tool for elucidating key aspects of cancer biology, and may provide important insights into the molecular mechanisms underlining the tumorigenesis process of prostate cancer. PCA3, is considered the most specific prostate cancer biomarker, however its biological role, until now, remained unknown. PCA3 is a long non-coding RNA (ncRNA) expressed from chromosome 9q21 and its study led us to the discovery of a novel human gene, PC-TSGC, transcribed from the opposite strand and in an antisense orientation to PCA3. With the work presented in this thesis, we demonstrate that PCA3 exerts a negative regulatory role over PC-TSGC, and we propose PC-TSGC to be a new tumor suppressor gene that contrasts the transformation of prostate cells by inhibiting Rho-GTPases signaling pathways. Our findings provide a biological role for PCA3 in prostate cancer and suggest a new mechanism of tumor suppressor gene inactivation mediated by non-coding RNA. Also, the characterization of PCA3 and PC-TSGC led us to propose a new molecular pathway involving both genes in the transformation process of the prostate, thus providing a new piece of the jigsaw puzzle representing the complex biology of prostate cancer.

0 Followers
 · 
74 Views
  • Genetics Research 09/1969; 14(1):53-61. DOI:10.1017/S0016672300001841 · 2.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mammalian genomes encode numerous natural antisense transcripts, but the function of these transcripts is not well understood. Functional validation studies indicate that antisense transcripts are not a uniform group of regulatory RNAs but instead belong to multiple categories with some common features. Recent evidence indicates that antisense transcripts are frequently functional and use diverse transcriptional and post-transcriptional gene regulatory mechanisms to carry out a wide variety of biological roles.
    Nature Reviews Molecular Cell Biology 08/2009; 10(9):637-43. DOI:10.1038/nrm2738 · 36.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recently, it was discovered that non-protein-coding RNAs (ncRNAs) represent the majority of the human transcripts. Regulatory role of many classes of ncRNAs is broadly recognized; however, long intronic ncRNAs have received little attention. In the past few years, evidence that intronic regions are key sources of regulatory ncRNAs has first appeared. Here we present an updated vision of the intronic ncRNA world, giving special attention to the long intronic ncRNAs. We summarize aspects of their expression pattern, evolutionary constraints, biogenesis, and responsiveness to physiological stimuli, and postulate their mechanisms of action. Deciphering nature's choice of different types of messages conveyed by ncRNAs will shed light on the RNA-based layer of regulatory processes in eukaryotic cells.
    Genomics 04/2009; 93(4):291-8. DOI:10.1016/j.ygeno.2008.11.009 · 2.79 Impact Factor

Preview

Download
1 Download