Post-transcriptional processing of genetic information and its relation to cancer

Abstract

During the development, progression and dissemination of neoplastic lesions, cancer cells hijack normal pathways and mechanisms, especially those involved in repair and embryologic development. These pathways include those involved in intercellular communication, control of transcription, post-transcriptional regulation of protein production including translation of mRNAs, post-translational protein modifications, e.g., acetylation of proteins, and protein degradation. Small, non-translatable RNAs, especially microRNAs (miRs), are Important components of post-transcriptional control. MiRs are produced from areas of the genome that are not translated into proteins, but may be co-regulated with their associated genes. MiRs bind to the 3’ untranslated regions of mRNAs and regulate the expression of genes in most cases by either promoting the degradation of mRNA and/or inhibiting the translation of mRNAs into proteins; thus, miRs usually cause a decrease in protein levels that would be expected if the mRNAs were translated normally. It is early in our understanding of how miRs affect neoplastic processes, but miRs are expressed differentially in most cancers and have been associated with tumor progression, chemoresistance and metastasis. MiRs are present in nanovesicles, such as exosomes, and thus are likely involved in intercellular communication, especially in neoplasia. MiRs are attractive targets for novel therapies of cancer as well as potential biomarkers that might be useful for early detection and diagnosis, and for prediction of therapeutic efficacy. MiRs also could aid and in determining prognosis, evaluating novel therapies, and developing preventive strategies by their use as surrogate end points.

Key words::

• biomarkers
• mRNA
• microRNA
• post-transcriptional regulation
• transcriptional regulation
• translation

Acknowledgments

Support provided in part by a grant to Lacey McNally, K99 Award R00 CA139050-03 and to William E. Grizzle from the Breast (5P50CA089019), Pancreatic (2P50CA101955) and Cervical (5P50CA098252) SPORES at the University of Alabama at Birmingham, the DOD Prostate Cancer grant (PC093309), the UAB Skin Diseases Research Center (P30AR50948), and the U54 MSM/TU/UAB Comprehensive Cancer Center Partnership (2U54CA118948).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.