Kaposi's sarcoma-associated herpesvirus infection induces overexpression of LYN in Kaposi's sarcoma

Kaposi's sarcoma-associated herpesvirus (KSHV) is an important pathogen for Kaposi's sarcoma (KS), a multiple hemangiosarcoma. We identified differentially expressed v-yes-1 Yamaguchi sarcoma viral related oncogene homolog (lyn) gene in Xinjiang Uyghurs KS tumor tissues and normal skin tissues by Affymetrix microarray. Analyzed the influence of KSHV infection on the expression of LYN gene in human umbilical vein endothelial cells (HUVECs) to characterize the pathogenesis of KS and identify therapeutic targets for KS. According to the microarray and bioinformatics, LYN up-regulated in KS tissues primarily participated in response to biotic stimulus, immune response and signal transducer activity. Moreover, LYN was over-expressed in KS tissues which confirmed by immunohistochemistry (IHC) and real-time PCR. KSHV infection was detected in blood serum of 72 Xinjiang Uyghurs KS patients including the patients who provided the tissues to do microarray and 68 normal people by amplification of KS330233. The seroprevalence of KSHV was 91.7% (66/72) in KS patients and 11.8% (14/68) in normal controls of Xinjiang province (P<0.001). To explore the relationship between LYN and KSHV, we extracted KSHV from BCBL-1 cells was used to infect primary cultured HUVECs. The levels of LYN in infected HUVECs and uninfected cells were evaluated by western blot. We noted that LYN was increased and a time-effect relationship with KSHV infection. Then infected cells were treated with a LYN inhibitor, PP2. PP2 inhibited LYN expression and decreased the cell viability (P<0.01) which was evaluated by western blot and Cell Counting Kit 8, respectively. Altogether the pathogenic mechanism of KSHV in KS may involve promotion of LYN overexpression in vascular endothelial cells.