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Delta bovine papillomaviruses (δBPVs) causes fibropapillomas or bladder cancer in cattle.  E5  is the major oncogene of δBPVs; however, the influence that  E5  oncogene has on host microRNA (miRNA) and mRNA expression profiles remains little elucidated. In the present study, small RNA sequencing and RNA sequencing were used to explore alterations in miRNAs and mRNAs in  E5  over-expressing Madin-Darby bovine kidney (MDBK) cells compared with controls. In total, 77 miRNAs (including 30 bovine-derived miRNAs) and 223 genes were differentially expressed (DE) following  E5  overexpression. The dysregulated genes were mainly involved in metabolic and biosynthetic processes. We constructed a potential miRNA-gene regulatory network from the differentially expressed genes (DEGs) and DE miRNAs. Finally, 22 DEGs and nine DE miRNAs were selected for RT-qPCR validation. Of these, downregulation of six miRNAs,  bta-miR-34c ,  bta-miR-122 ,  bta-miR-195 ,  bta-miR-449b ,  bta-miR-2425-5p , and  bta-miR-2428-3p  were confirmed; In addition, upregulation of 16 genes,  ACSS2 ,  DDIT4 ,  INHBE ,  INSIG1 ,  PNRC1 ,  PSAT1 ,  PSPH ,  PYCR1 ,  SC4MOL ,  SLC34A2 ,  SCD ,  SPARC ,  IDI1 ,  PCK2 ,  HMGCS1 , and  SMIM14  and downregulation of two genes,  BATF3  and  WFDC2  were confirmed. Specially,  bta-miR-34c  and  bta-miR-449b  potentially regulated  PYCR1  and  DDIT4 , which were involved in cancer progression and angiogenesis. Our study presented for the first time the comprehensive miRNA and mRNA alterations in MDBK cells expressing the BPV  E5  oncogene, providing new insights into the tumorigenesis induced by BPV E5.

Comprehensive analysis of differentially expressed microRNAs and mRNAs in MDBK cells expressing bovine papillomavirusE5oncogene