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

Abstract

Delta bovine papillomaviruses (δBPVs) causes fibropapillomas or bladder cancer in cattle.E5is the major oncogene of δBPVs; however, the influence thatE5oncogene 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 inE5over-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) followingE5overexpression. 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, andbta-miR-2428-3pwere confirmed; In addition, upregulation of 16 genes,ACSS2,DDIT4,INHBE,INSIG1,PNRC1,PSAT1,PSPH,PYCR1,SC4MOL,SLC34A2,SCD,SPARC,IDI1,PCK2,HMGCS1, andSMIM14and downregulation of two genes,BATF3andWFDC2were confirmed. Specially,bta-miR-34candbta-miR-449bpotentially regulatedPYCR1andDDIT4, 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 BPVE5oncogene, providing new insights into the tumorigenesis induced by BPV E5.