A Decade of Global mRNA and miRNA Profiling of HPV-Positive Cell Lines and Clinical Specimens

Abstract

For more than a decade, global gene expression profiling has been extensively used to elucidate the biology of human papillomaviruses (HPV) and their role in cervical- and head-and-neck cancers. Since 2008, the expression profiling of miRNAs has been reported in multiple HPV studies. Two major strategies have been employed in the gene and miRNA profiling studies: In the first approach, HPV positive tumors were compared to normal tissues or to HPV negative tumors. The second strategy relied on analysis of cell cultures transfected with single HPV oncogenes or with HPV genomes compared to untransfected cells considered as models for the development of premalignant and malignant transformations.In this review, we summarize what we have learned from a decade of global expression profiling studies. We performed comprehensive analysis of the overlap of the lists of differentially expressed genes and microRNAs, in both tissue samples and cell culture based studies. The review focuses mainly on HPV16, however reports from other HPV species are used as references. We discuss the low degree of consensus among different studies and the limitation of differential expression analysis as well as the fragmented miRNA-mRNA target correlation evidence. Furthermore, we propose an approach for future research to include more comprehensive miRNA-mRNA target correlation analysis and to apply systems biology/gene networks methodology.

Clinical implications of (epi)genetic changes in HPV-induced cervical precancerous lesions

“…HPV 68 has been classified as probable high-risk (also known as IARC class 2A) and another seven types have been classified as possible high-risk (HPV 26,53,66,67,70,73 and 82;also known as IARC class 2B) 5 .…”

microRNAs are biomarkers of oncogenic human papillomavirus infections

“…Previously, our group and others found that HPV infection regulates the expression of keratinocyte miRNAs (18)(19)(20) and that aberrant miRNA expression in CC and its derived cell lines is important for cancer cell proliferation (21)(22)(23)(24). However, the different approaches used led to varied observations (25,26). To date, there is no systematic study to identify host miRNAs as specific biomarkers for diagnosis of HPV infection or progression.…”

Differential Expression of MicroRNAs in Uterine Cervical Cancer and Its Implications in Carcinogenesis; An Integrative Approach

“…An earlier study on the global mRNA and miRNA profiling in HPV-positive cell lines observed that different HPV types in dissimilar biological conditions may also affect the same pathway, but genes involved may be different. 24 Similarly, another study on the role of miRNA in HPV-associated cancers indicated that a set of miRNAs was shared exclusively by HPV-positive head and neck squamous cell carcinoma and cervical squamous cell carcinoma compared with the number of miRNAs shared exclusively by HPV-negative head and neck squamous cell carcinoma and cervical squamous cell carcinoma. 25 Thus, all these data show that carcinogenic mechanism may be similar in HR-HPV infection irrespective of different HPV types.…”