Human papillomaviruses (HPVs) are associated with the pathogenesis of a variety of human cancers, including cervical and oropharyngeal cancers. The HPV E6 and E7 oncogenes are usually expressed to high levels in these cancers. Previous studies have shown dysregulation of cellular microRNAs (miRNAs) in HPV-positive cell lines and cancer tissues and recent studies have identified a few miRNAs whose levels are altered in the presence of the viral E6 and E7 proteins. In order to identify all the cellular miRNAs whose expression may be affected by these oncoproteins, we carried out microarray analysis using human foreskin keratinocytes (HFKs) expressing either or both of these two proteins. These studies showed that 90 and 60 miRNAs were dysregulated in the presence of the E6 or the E7 protein, respectively. Of these, 43 miRNAs were similarly affected in HFK-E6 and/or HFK-E7 when compared to control cells. The joint expression of E6 and E7 proteins in HFKs caused changes in the levels of 64 miRNAs, of which 24 were similarly affected in HFK-E6 and/or HFK-E7 cells relative to controls. The microarray experiments were validated by quantitative real-time RT-PCR analysis of several differentially expressed miRNAs. Several miRNAs dysregulated by the E6 and/or E7 proteins are known to be altered in a variety of human cancers. Furthermore, previously known cellular targets of these miRNAs are involved in processes such as cell cycle regulation, apoptosis, cell-cell adhesion, cell mobility and proliferation, and alterations in their levels may contribute to HPV-associated carcinogenesis. Taken together, the results of our studies suggest that high risk HPV E6 and E7 proteins share the ability to regulate a subset of cellular miRNAs.

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The reduction of mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin con centration (MCHC) whereas increasing of reticulocytes number and indirect bilirubin after 20 weeks of experiment of dimethylhydrazine (DMH) induced colon carcinogenesis indicate the hemolysis of red blood cells due to the DMH influence during tumor development. The slight increasing of number of monocytes and platelets, as well as considerable increasing of a number of eosinophilic granulocytes, has been observed. Reduction of number of hemoglobin and erythrocytes, slight increase of number of monocytes, and signifi cant increase in number of platelets in blood of rats follows 26 weeks of the experiment (after 6 weeks of DMH discontinuation). Anemia with thrombocytosis accompany cancer in humans and the model of DMH induced colon cancer is appropriate not only for studies of carcinogenesis and searching of new antineoplastic drugs but also for the development of correctional approaches of cancer associated changes in the hemato poietic system.

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