SPP1 rs4754 and its epistatic interactions with SPARC polymorphisms in gastric cancer susceptibility
GENE
Authors: Chen, Le-zong; He, Cai-yun; Su, Xuan; Peng, Jun-Ling; Chen, Dong-liang; Ye, Zulu; Yang, Dong-dong; Wang, Zi-xian; Wang, Feng; Shao, Jian-yong; Xu, Rui-hua
Abstract
The matricellular glycoprotein products of the SPP1 and SPARC genes play critical roles in many aggressive tumor phenotypes including gastric cancer. We sought to test whether the polymorphisms of these two genes, individually or jointly, influence gastric cancer susceptibility. Nine potentially functional, tagging single nucleotide polymorphisms (tagSNPs) of SPP1 and SPARC were selected and detected using the Kompetitive Allele Specific PCR method in 301 gastric cancer cases and 1441 healthy control subjects. We found that the genotype frequencies of SPP1 rs4754 in gastric cancer were significantly different from those in controls. The rs4754 TT genotype conferred an increased risk of gastric cancer, with unadjusted and adjusted ORs ranging from 1.75 to 1.95 (all P < 0.05). The assessment of the effect modifications of sex and age on the genetic effects also confirmed the statistically significant association of the rs4754 TT genotype with increased gastric cancer risk. Epistatic interactions were found between SPP1 rs4754 and SPARC rs1054204, rs3210714 and rs3549 (all P values for interaction < 0.05). During the assessment of the epistatic effects between pairs of interacting factors, increased gastric cancer risk was observed in the combined presence of the SPP1 rs4754 TT genotype and the common genotypes of interacting SPARC SNPs, with ORs ranging from 3.94 to 4.41. When the genetic influence of SPP1 rs4754 TT was excluded, the genetic effects of the SPARC rs1054204, rs3210714 and rs3549 common genotypes on gastric cancer susceptibility switched from being risky to beneficial. These data reveal an association between the SPP1 rs4754 polymorphism and altered risk of gastric cancer and highlight an important role of the epistatic effects of SPP rs4754 with SPARC polymorphisms in gastric carcinogenesis. Additional functional experiments and independent large-scale studies, especially in other ethnic populations, are needed to confirm our results.
Comparative transcriptome analysis of the main beam and brow tine of sika deer antler provides insights into the molecular control of rapid antler growth
CELLULAR & MOLECULAR BIOLOGY LETTERS
Authors: Yao, Baojin; Wang, Chaonan; Zhou, Zhenwei; Zhang, Mei; Zhao, Daqing; Bai, Xueyuan; Leng, Xiangyang
Abstract
Background: Deer antlers have become a valuable model for biomedical research due to the capacities of regeneration and rapid growth. However, the molecular mechanism of rapid antler growth remains to be elucidated. The aim of the present study was to compare and explore the molecular control exerted by the main beam and brow tine during rapid antler growth. Methods: The main beams and brow tines of sika deer antlers were collected from Chinese sika deer (Cervus nippon) at the rapid growth stage. Comparative transcriptome analysis was conducted using RNA-Seq technology. Differential expression was assessed using the DEGseq package. Functional Gene Ontology (GO) enrichment analysis was accomplished using a rigorous algorithm according to the GO Term Finder tool, and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis was accomplished with the R function phyper, followed by the hypergeometric test and Bonferroni correction. Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to verify the RNA levels for differentially expressed mRNAs. Results: The expression levels of 16 differentially expressed genes (DEGs) involved in chondrogenesis and cartilage development were identified as significantly upregulated in the main beams, including transcription factor SOX-9 (Sox9), collagen alpha-1(II) chain (Col2a1), aggrecan core protein (Acan), etc. However, the expression levels of 17 DEGs involved in endochondral ossification and bone formation were identified as significantly upregulated in the brow tines, including collagen alpha-1(X) chain (Col10a1), osteopontin (Spp1) and bone sialoprotein 2 (Ibsp), etc. Conclusion: These results suggest that the antler main beam has stronger growth capacity involved in chondrogenesis and cartilage development compared to the brow tine during rapid antler growth, which is mainly achieved through regulation of Sox9 and its target genes, whereas the antler brow tine has stronger capacities of endochondral bone formation and resorption compared to the main beam during rapid antler growth, which is mainly achieved through the genes involved in regulating osteoblast and osteoclast activities. Thus, the current research has deeply expanded our understanding of the intrinsic molecular regulation displayed by the main beam and brow tine during rapid antler growth.