Genome-wide transcriptome analysis of KSHV long-term-infected endothelial (LTC) and parental uninfected TIVE cells [RNA-seq]

Purpose: To characterize genome-wide mRNA expression profiles in the context of Kaposi’s sarcoma-associated herpesvirus (KSHV)-induced oncogenesis using isogenic cell lines for a Kaposi's sarcoma (KS) xenograft model: KSHV-infected human endothelial cells (LTC) that form tumors with properties closely resembling KS lesions in nude mice and uninfected parental (TIVE) cells. Methods: mRNA expression profiles of LTC and TIVE cells were generated by deep sequencing using Illumina. In addition, mRNA profiles of LTC transfected with miR-127-3p or negative control (NC) mimic were generated by deep sequencing. Results: We analyzed global transcriptome changes in LTC compared to TIVE cells and identified significant upregulation of many cell cycle and oncogenic signaling pathways. In addition, we assessed global transcriptome changes in LTC transfected with miR-127-3p mimic and found a significant decrease in the levels of E2F and Myc targets, indicating that miR-127-3p suppresses E2F and Myc transcriptional activities. Conclusions: This study provides a detailed analysis of the cellular transcriptome in LTC and TIVE cells using RNA sequencing technology. Our study identifies miR-127-3p as a potent tumor suppressor miRNA that acts as a negative regulator of the CDK-RB-E2F cell cycle signaling pathway and the oncogenic Myc network in the context of KSHV oncogenesis and establishes a strong rationale for developing this miRNA as a therapeutic agent against KS. mRNA profiles of LTC and TIVE cells were generated by deep sequencing using Illumina. In addition, mRNA profiles of LTC treated with miR-127-3p or NC mimic were generated using deep RNA-seq.