Long non-coding RNAs (LncRNAs), viral oncogenomics, and aberrant splicing events : therapeutics implications

Abstract

It has been estimated that worldwide up to 10% of all human cancers are the result of viral infection, with 7.2% of all cancers in the developed world have a viral aetiology. In contrast, 22.9% of infections in the developing world are the result of viral infections. This number increases to 30% in Sub-Saharan Africa. The ability of viral infections to induce the transformation of normal cells into cancerous cells is well documented. These viruses are mainly Hepatitis B and C viruses, Epstein Barr virus, Human papillomavirus and Human Cytomegalovirus. They can induce the transformation of normal cells into cancer cells and this may be the underlying cause of carcinogenesis in many different types of cancer. These include liver cancer, lymphoma, nasopharyngeal cancer, cervical cancer, gastric cancer and even glioblastoma. Long non-coding RNAs (LncRNAs) can function by regulating the expression of their target genes by controlling the stability of the target mRNAs or by blocking translation of the target mRNA. They can control transcription by regulating the recruitment of transcription factors or chromatin modification complexes. Finally, lncRNAs can control the phosphorylation, acetylation, and ubiquitination of proteins at the post-translation level. Thus, altering protein localisation, function, folding, stability and ultimately expression. In addition to these functions, lncRNA also regulate alternate pre-mRNA splicing in ways that contribute to the formation of tumours. This mainly involves the interaction of lncRNAs with splicing factors, which alters their activity and function. The ability of lncRNAs to regulate the stability, expression and function of tumour suppressor proteins is important in the development and progression of cancers. LncRNAs also regulate viral replication and latency, leading to carcinogenesis. These factors all make lncRNAs ideal targets for the development of biomarker arrays that can be based on secreted lncRNAs leading to the development of affordable non-invasive biomarker tests for the stage specific diagnosis of tumours. These lncRNAs can also serve as targets for the development of new anticancer drug treatments.