SET domain containing (lysine methyltransferase) 8 (Setd8), a histone modification enzyme, affects cell cycling, chromosome condensation, high efficient repair of DNA double strand breaks and so on. The objective of this study was to identify novel alternative splicing variants of pig Setd8 gene and its mRNA expression. Four 180-day-old male Guanzhong Black (GZB) pigs and six male Landrace piglets (including three 30-day-old and three 7-day-old pigs) were collected to study Setd8 gene. Herein, two novel variants, Setd8a and Setd8b, were found in pig. The entire sequences of Setd8a and Setd8b variants were 1,039 bp and 958 bp, respectively. qRT-PCR results showed that Setd8a and Setd8b were highly expressed in brains and testes of 180-day-old GZB pigs. Moreover, the expressions of the two Setd8 variants were significantly higher in testis than brain of GZB pig (P < 0.05). Further study on testis showed that the mRNA expression of Setd8a variant was significantly lower than Setd8b variant in 30-day-old and 7-day-old pigs (P < 0.05). The mRNA expression of Setd8a variant'was lower than Setd8b variant in GZB pigs (P > 0.05). Moreover, the expressions of the two Setd8 variants were significantly higher along with age enlargement. In conclusion, Setd8a and Setd8b were firstly identified in pigs and both were expressed in pig testis. Setd8b was the major splicing variant of pig Seid8 gene transcript product. Moreover, the expressions of Setd8 variants were time-dependent. All these findings would enrich the study of Setd8 gene in pig testis.
Numerous topoisomerase inhibitors with proven efficacy have been used extensively to treat various human neoplasms. However, among these, only doxorubicin has been used and studied extensively in veterinary oncology. The current study was performed to evaluate the responsiveness of canine osteosarcoma (cOSA), mammary gland tumour (cMGT), and malignant melanoma (cMM) cell lines to several topoisomerase inhibitors. In addition, the correlation between the sensitivity to treatment and multi-drug resistant (MDR) factors was investigated. cOSA cell lines exhibited higher sensitivity than cMGT and cMM cell lines to all the topoisomerase inhibitors tested in vitro; this was associated with the levels of multi-drug resistance protein 1 (MDR1) gene expression in the cOSA cell lines. Treatment of cOSA (HMPOS) and cMGT cell line (CHMp) xenograft mouse models with etoposide markedly delayed tumour progression in HMPOS xenografts, but failed to elicit lasting anti-tumour effects on CHMp xenograft mice. The present findings suggest that MDR1 represents a molecular signature for prediction of treatment efficacy of topoisomerase inhibitors, especially that of etoposide, which may be a clinically useful anti-tumour agent for cOSA; however, further study is necessary to refine the treatment protocol.