The recent discovery of different classes of non-coding RNAs and their importance in almost every cellular process has opened a new frontier in understanding the regulation of gene expression. The main interest in my laboratory is to study the importance of non-coding RNAs, such as microRNAs (miRNAs) and large intergenic non-coding RNAs (lincRNAs), during the process of carcinogenesis in cells infected by human papillomaviruses (HPVs).
miRNAs are double-stranded ~22 nt RNAs that can base-pair with specific messenger RNA (mRNA) targets and regulate their expression by translational repression or mRNA degradation. Many different miRNAs have been implicated in human cancers, either as oncogenic miRNAs or tumor suppressor miRNAs. In addition, viruses have been associated with 15-20% of all cancers and previous studies have shown that the expression of HPV oncogenes can regulate host miRNAs (such as miR-218) and influence the transcriptional profile of the infected cells. One of the biggest challenges in the miRNA field is to determine the mRNA targets of all miRNAs. By using a technology known as HITS-CLIP (high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation) my lab studies the global interactions between miRNAs and their targets during infection and transformation by HPV in head and neck cancers.
LincRNAs (another class of non-coding RNAs recently discovered) have the ability to regulate gene expression by directly interacting with chromatin-modifying proteins and helping them target specific genomic regions at distant loci. By using global lincRNA expression assays, reporter constructs, mutational and biochemical analyses, as well as functional assays, my lab also wants to explore the importance of lincRNAs in HPV-related cancers. HPV, like most oncogenic viruses, modulate a subset of specific cellular pathways: cell cycle regulation, apoptosis and cellular senescence (a form of irreversible growth arrest and a major tumor suppressor mechanism). Interestingly, the repression of the HPV viral oncogenes in cervical carcinoma cell lines reactivates the expression of the tumor suppressor proteins p53 and Rb which leads to a rapid induction of senescence. Thus, we are also interested in studying the differences in miRNA and lincRNA expression and processing pathways during senescence and other types of growth arrest such as quiescence.
Sara Crile Allen and James Frederick Allen Lung Cancer (Emerging)
Understanding the importance of non-coding RNAs in human papillomavirus-related cancers and models of growth arrest