Specific types of human papillomaviruses (HPVs) cause cervical cancer. Cervical cancers exhibit aberrant cellular microRNA (miRNA) expression patterns. By genome-wide analyses, we investigate whether the intracellular and exosomal miRNA compositions HPV-positive cancer cells are dependent on endogenous E6/E7 oncogene expression. Deep sequencing studies combined with qRT-PCR analyses show that silencing significantly affects ten 52 most abundant miRNAs in HPV18-positive HeLa cells,...

Certain types of human papillomaviruses (HPVs) are closely linked to the development cancers. Herein, it is shown that intracellular targeting HPV16 E6 oncoprotein by E6-binding peptide aptamers resulted in apoptotic elimination HPV16-positive cancer cells, whereas HPV-negative cells were not affected. These results provide direct experimental evidence HPV has antiapoptotic activity HPV-positive tumor required for their survival. The E6-targeting molecules identified herein have implications...

Abstract Background The enhancer of zeste homolog 2 ( EZH2 ) gene exerts oncogene-like activities and its (over)expression has been linked to several human malignancies. Here, we studied a possible association between expression prognosis in patients with renal cell carcinoma (RCC). Methods protein RCC specimens was analyzed by immunohistochemistry using tissue microarray (TMA) containing tumor corresponding normal samples 520 patients. For immunohistochemical assessment expression, nuclear...

The four Rep proteins encoded by adeno-associated virus type 2 (AAV-2) inhibit transcription of their own promoters and several heterologous promoters. To gain insight into the molecular mechanism Rep-mediated repression, we studied effects on accumulation mRNA transcribed from human papillomavirus 18 upstream regulatory region HPV18 URR, immunodeficiency long terminal repeat, AAV-2 p5 p19 transient transfection experiments in HeLa cells. We observed a distinct contribution C- N-terminal...

Somatic mutations in the p53 tumor suppressor gene represent single most common genetic alteration observed human cancers. Interestingly, great majority of malignant tumors cervix uteri contain wild-type alleles together with DNA specific types papillomaviruses (HPVs), while small portion HPV-negative cervical carcinomas often carry alterations gene. Transcriptional activation yet-undefined cellular regulatory genes has been implicated to play a key role for tumor-suppressive activity p53,...

The transcription factor signal transducer and activator of (Stat) 3 is activated through the interleukin-6 family cytokines by binding growth factors to epidermal (EGF) receptor. It plays an essential role in embryonic development assumes specialized tasks many differentiated tissues. Constitutively Stat3 has been found tumor cell lines primary tumors a crucial survival proliferation. To inhibit oncogenic action cells, we have selected short peptides, so-called peptide aptamers, which...

The malignant transformation potential of high-risk human papillomaviruses (HPVs) is closely linked to the expression viral E6 and E7 genes. To elucidate molecular mechanisms resulting in HPV oncogene expression, a systematic analysis cis-regulatory elements within type 18 (HPV18) upstream regulatory region (URR) which regulate activity E6/E7 promoter was performed. As functional behavior given element can be strongly influenced by overall composition transcriptional control region,...

Abstract The malignant phenotype of human papillomavirus (HPV)-positive cancer cells is maintained by the activity viral E6 and E7 genes. Here, we identified polycomb group gene enhancer zeste homologue 2 (EZH2) as a novel downstream target for oncogenes in HPV-transformed cells. EZH2 expression was activated HPV16 at transcriptional level via E7-mediated release E2F from pocket proteins. RNA interference analyses showed that continuous required proliferation HPV-positive tumor stimulating...

The human papillomavirus (HPV) E6/E7 oncogenes play a crucial role in the HPV-induced carcinogenesis. In this study, authors investigated whether silencing of endogenous HPV expression may influence contents or amounts extracellular microvesicles (eMVs) released from HPV-positive cancer cells. It was found that eMVs secreted HeLa cells are enriched for Survivin protein. RNA interference studies revealed maintenance both intracellular and microvesicular strongly dependent on continuous...

The Enhancer of Zeste 2 (EZH2) protein has been reported to stimulate cell growth in some cancers and is therefore considered represent an interesting new target for therapeutic intervention. Here, we investigated a possible role EZH2 the control colon cancer cells. RNA interference (RNAi)-mediated intracellular depletion led cycle arrest carcinoma cells at G1/S transition. This was associated with reduction numbers upon transient transfection synthetic EZH2-targeting siRNAs inhibition their...

The E6 gene of tumor-associated types human papillomaviruses codes for a functional antagonist p53. Overexpression from heterologous promoters can block p53-mediated cellular responses to DNA damage, such as transcriptional stimulation p53 target genes and cell-cycle arrest in G1. In contrast, genotoxic treatment HPV-positive cancer cells, which express the chromosomally integrated viral copies, results increased expression p21WAF1 and, several cell lines, induction G1 arrest. present study,...

Oncogenic human papillomaviruses (HPVs) are closely linked to major malignancies, including cervical and head neck cancers. It is widely assumed that HPV-positive cancer cells under selection pressure continuously express the viral E6/E7 oncogenes, their intracellular p53 levels reconstituted on repression, inhibition phenotypically results in cellular senescence. Here we show hypoxic conditions, as often found subregions of cancers, enable escape from these regulatory principles:...

The HPV E6 oncoprotein maintains the malignant phenotype of HPV-positive cancer cells and represents an attractive therapeutic target. forms a complex with cellular E6AP ubiquitin ligase, ultimately leading to p53 degradation. recently elucidated x-ray structure HPV16 E6/E6AP showed that distinct binding pocket for E6AP. This discovery raises question whether is druggable, i. e. it provides docking site functional inhibitors. To address these issues, we performed detailed analysis...