Transcriptomic analyses of genes differentially expressed by high-risk and low-risk human papilloma virus E6 oncoproteins

Abstract

Human papilloma virus is the causative agent for cervical cancer with 99 % of cervical cancer cases containing HPV. The high risk HPV-16, 18 and 31 are the major causative agents. The low risk HPV-6, 11 have been reported to cause penile, laryngeal, bronchogenic and oesophageal cancer. Since E6 oncoprotein is frequently over expressed in cancers, we did gene expression studies to compare between the E6 genes of high-risk (HPV18) or low-risk (HPV11)stably transfected in epithelial cell line EPC-2 or mock transfected with the basic vector pCDNA3.1. Microarray studies showed a total of 697 genes showing differential expression between the samples. Genes involved in several key cellular processes such as cell adhesion, angiogenesis, transcription regulation, cell cycle regulation and cell division showed altered expression between the samples. Gene Ontology mapping of 44 genes according cellular pathways revealed 13 pathways namely angiogenesis, alzhemier's, Wnt, p53, interleukin, TGF-b, cadherin, integrin, PI3-kinase, catennin, insulin, chemokine and G protein signalling pathways. The microarray results were confirmed by quantitative real-time PCR for some representative genes like IFI27, CTNNA1, OSMR, CYP1B1, TNFSF13, LAMA2 and COL5A3. Analysis of differentially expressed genes by high-risk and lowrisk HPV E6 proteins might help in identification of potential biomarkers for diagnosis, progression and therapy of oesophageal cancer. The understanding of mechanisms of activation of these genes as well as the function of gene products will give a further insight into their roles in oesophageal cancer.

Analysis of Differentially Expressed Genes in a Chinese Cohort of Esophageal Squamous Cell Carcinoma

“…Amongst the differentially expressed ESCC genes identified, some hits have been highlighted in previous studies, including MCM4, MMP1, MMP12, SLC22A3 along with members of the CLIC family [25][26][27]. Furthermore, based on the results of the GSEA analysis, p53 pathways along with cell cycle regulation were also de-regulated in ESCC, a finding that had been reported previously [28]. For validating our datasets we chose the CLIC family of genes, not because they represented the most highly over-or under-expressed genes in ESCC.…”

Lectin-Like Transcript 1 (LLT1) Checkpoint: A Novel Independent Prognostic Factor in HPV-Negative Oropharyngeal Squamous Cell Carcinoma

“…On the other hand, our data unveil a possible link between LLT1/CLEC2D expression and HPV infection. In line with this, CLEC2D expression was found to be upregulated by HPV E6 oncoprotein [23]. Similarly, it has also been demonstrated that PD-L1 expression is induced by HPV16 E7 oncoprotein, thereby leading to antitumor response inhibition in cervical cancer [24].…”

Expression of Cell Cycle-related Proteins p16, p27 and Ki-67 Proliferating Marker in Laryngeal Squamous Cell Carcinomas and in Laryngeal Papillomas

“…Despite the fact that the association between HPV infection and benign as well malignant lesions of the upper respiratory tract has been already well documented, there are still ambiguities of the pathways leading to the malignant transformation of the cells (8,(17)(18)(19).…”