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Simple Summary: Chinese Holstein cattle are the main breed of dairy cows in China. This work performed an association analysis between polymorphisms of three candidate genes (ABCG2, CD44, SPP1) and milk production performance on Chinese Holstein cattle. The results showed that the different genotypes of these 10 SNPs from the ABCG2, CD44, and SPP1 genes significantly affected the milk production performance of Chinese Holstein cattle in terms of milk yield, milk fat percentage, milk protein percentage, somatic cell score, and urea nitrogen content. The ABCG2, CD44, and SPP1 genes could be selected for marker-assisted selection, which is of great significance for future precise molecular breeding. Based on our results of genome-wide association analysis, we performed gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis; three candidate genes (ABCG2, CD44, SPP1) were screened in this study for SNPs association analysis with production traits in 999 Holstein cattle. In this research, flight mass spectrometry genotyping was used to detect the polymorphism of SNP seats. It was shown that four, four, and two single nucleotide polymorphisms (SNP) loci were detected for the ABCG2, CD44, and SPP1 genes, respectively, and the different genotypes of these 10 SNPs significantly affected the milk production performance of Chinese Holstein cattle in terms of milk yield, milk fat percentage, milk protein percentage, somatic cell score, and urea nitrogen content. Among them, ABCG2-G.80952G > T locus, ABCG2-G.120017G > A locus and CD44-G.2294G > C locus had significant effects on somatic cell score (p < 0.01). Cows with GG genotypes at ABCG2-G.80952G > T locus, AA and GG genotypes at ABCG2-G.120017G > A locus, and GG genotypes at CD44-G.2294G > C locus had lower somatic cell scores. The present study elucidated that ABCG2, CD44, and SPP1 could be selected for marker-assisted selection and will benefit for future precise molecular breeding. [ABSTRACT FROM AUTHOR]

Siraitia grosvenorii is the fruit of a cucurbitaceous vine endemic to China. Its extract has been used as a sweetener and exhibits various anti-inflammatory and anticarcinogenic effects mediated via its antioxidant properties. In the present study, we aimed to clarify the preventive or ameliorative effects of S. grosvenorii extract (SGE) on nonalcoholic steatohepatitis-like lesions induced in male Hsd: Sprague Dawley rats fed a choline-deficient, methionine-lowered, L-amino acid-defined diet for 13 weeks. This diet increased hepatotoxicity parameters and upregulated the expression of inflammation- and fibrosis-related genes in the liver, resulting in the progression of hepatic lesions, oxidative stress, hepatocellular apoptosis, and fibrosis. Furthermore, this diet upregulated the expression of phosphorylated nuclear factor-xB (NF-kB) and CD44. SGE administration inhibited these lesions, similar to CD44, a factor that controls hepatic inflammation and fibrosis. These results revealed that SGE impacts the disease stage via antioxidative effects and regulation of CD44 expression. SGE was found to be useful for preventing and treating steatohepatitis. [ABSTRACT FROM AUTHOR]

Simple Summary: There is an urgent need to find an effective therapeutic target for pancreatic cancer owing to late diagnosis, tumor metastasis, and current ineffective targeted drugs. We aimed to identified potential targets for the treatment of pancreatic cancer. In this study, the specific mechanism by which the CDCA8 contributes to pancreatic cancer progression via the activation of CD44 was clarified, and CDCA8 knockdown inhibited the proliferation and metastasis of pancreatic cancer. This finding may provide a promising target for future targeted therapies of pancreatic cancer. (1) Background: Recently, cell division cycle associated 8 (CDCA8) was found to be overexpressed in pancreatic ductal adenocarcinoma (PDAC). Here, we aimed to explore the specific mechanism of action of CDCA8 in PDAC progression. (2) Methods: All human PDAC samples and clinical data were collected from Huashan Hospital, Fudan University. All experimental studies were carried out using many in vitro and in vivo assays, including lentiviral transfection, real-time quantitative polymerase chain reaction (qPCR), western blotting, co-immunoprecipitation (Co-IP), chromatin IP (ChIP)-qPCR, dual-luciferase reporter, and in vivo imaging assays. (3) Results: Clinical data analysis of human PDAC samples revealed that CDCA8 overexpression were positively and negatively associated with tumor grade (p = 0.007) and overall survival (p = 0.045), respectively. CDCA8 knockdown inhibited PDAC proliferation and invasion in in vitro and in vivo assays. CD44 was also up-regulated by CDCA8 during PDAC progression. CDCA8 could be combined with SNAI2 to form a CDCA8/SNAI2 complex to integrate with the CD44 promoter as indicated through ChIP-qPCR and dual-luciferase reporter assays. (4) Conclusion: We showed that CDCA8-CD44 axis plays a key role in the proliferation and invasion of PDAC, which provides a potential target for treatment. [ABSTRACT FROM AUTHOR]

Purpose: (1) To investigate associations between single nucleotide polymorphisms (SNPs) in osteopontin (OPN) and its receptor-cluster of differentiation 44 (CD44) genes and gastric cancer susceptibility. (2) To explore the correlation of OPN and CD44 expression of gastric cancer. Methods: We detected 26 SNPs of the genes in gastric cancer patients from the Chinese Han population by Sequenom technique and performed expression of OPN in combination with CD44 in 243 tissues samples of the cases by tissue microarray and immunohistochemistry (IHC). Results: We found that the minor alleles of OPN rs4754C>T and OPN rs9138C>A remained strongly associated with decreased gastric cancer risk ( P = 1.53 × 10, odds ratio (OR) 0.642, 95 % confidence interval (CI) 0.511-0.808 and P = 1.59 × 10, OR 0.642, 95 %CI 0.510-0.809). OPN variant rs1126772A>G and CD44 variant rs353639A>C significantly contributed to elevated risk of gastric cancer ( P = 0.042, OR 1.279, 95 % CI 1.008-1.622 and P = 0.047, OR 1.334, 95 % CI 1.003-1.772). Haplotypes of OPN and CD44 variants significantly influenced risk of gastric cancer. Clinical data indicated that rs4754 and rs9138 of OPN were significantly associated with smoking ( P = 0.029, OR 0.343, 95 % CI 0.127-0.926 and P = 0.029, OR 0.343, 95 %CI 0.127-0.926) and OPN rs1126772 revealed associations with tumor-node-metastasis (TNM) stage ( P = 0.025, OR 1.765, 95 % CI 1.073-2.905) and tumor differentiation ( P = 0.031, OR 1.722, 95 % CI 1.049-2.825). OPN expression was observed in 133 of the 243 cases (54.7 %) by IHC and was correlated with serosa invasion ( P = 0.013), TNM stage ( P = 0.003) and lymph node metastasis ( P = 0.002). CD44 expression was found in 92 of the 243 cases (37.9 %) and was associated with tumor size ( P = 0.005) and lymph node metastasis ( P = 0.023), respectively. The OPN expression displayed a positive association with CD44 ( P = 0.01, r = 0.164). Conclusions: We found that the polymorphisms rs4754, rs9138 and rs1126772 of OPN gene and rs353639 of CD44 gene were significantly associated with gastric cancer. Our IHC data indicated that interaction of OPN and CD44 protein would promote progression and metastasis of gastric cancer. [ABSTRACT FROM AUTHOR]

The cell surface adhesion receptor CD44 reportedly affects the development and progression of cancers. Moreover, CD44 gene rs187115 polymorphism appears to be genetic determinant of cancer susceptibility. We investigated whether CD44 rs187115 polymorphism is associated with colorectal cancer (CRC) risk and prognosis. We enrolled 669 CRC cases and 826 controls in this three-center case-control study in a Chinese Han population. All individuals were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Cross-over analysis, multivariate logistic regression, Kaplan-Meier method, and Cox regression analysis were used for analysis. In this study, CD44 rs187115 polymorphism was associated with increased risk for CRC. Stratified analyses revealed that CD44 rs187115 polymorphism was correlated with increased risk for CRC in females, drinkers, smokers, and those aged ≥ 60 years. In addition, rs187115 polymorphism was significantly associated with TNM III+IV stage, lymph node metastasis and tumor size in CRC patients. Combined effects of CD44 rs187115 polymorphism (GG/AG vs. AA) and environmental factors (smoking and drinking) further increased the risk of CRC. GG genotype carriers showed poorer overall survival than AA genotype carriers. Cox regression analysis showed that drinking, CD44 rs187115 polymorphism, and TNM stage were independent prognostic factors affecting CRC. These findings show that CD44 rs187115 polymorphism may be a potential biomarker predictive of CRC susceptibility and prognosis.

Background: This study aimed to determine whether CD44 polymorphisms were correlated with hepatocellular carcinoma (HCC) and to reveal a new potential target for early prediction, prevention, and diagnosis of HCC., Method: This study involved 96 cases with chronic hepatitis B (CHB), 96 cases with hepatitis B virus-related liver cirrhosis (LC), 204 cases with HCC related to the hepatitis B virus, and 210 healthy controls. The genotype of rs8193 was determined using the restriction fragment length polymorphism method, while the genotypes of rs10836347 and rs13347 were determined by direct sequencing., Results: The results showed that patients with the CD44 rs13347 TT and T allele polymorphisms exhibited higher risks of LC than those carrying the CC genotype and C allele. The CD44 rs13347 CT and TT genotypes and T allele were significantly associated with an increased risk of HCC after adjusting for gender, age, smoking, and alcohol consumption (for CT: odds ratio [OR] = 1.626, 95% confidence interval [CI] = 1.057-2.500, P = .027; for TT: OR = 1.965, 95% CI = 1.043-3.702, P = .037; and for T: OR = 1.461, 95% CI = 1.091-1.956, P = .011). In the rs13347 site of the female population, the CT and TT genotypes were related to the high occurrence of HCC. In the population aged ≥50 years, carriers of the CD44 rs13347 CT and TT alleles were more susceptible to HCC compared with CC carriers. Those who consumed alcohol who carried the rs10836347 CT genotype exhibited a risk factor for HCC., Conclusion: For the CD44 rs13347 site, mutations in the T allele might be a risk factor for HCC., (© 2019 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.)

The rs187115, an intronic variant of CD44 gene, has been previously reported to play a potential role in genetic susceptibility to cancer. Here, we comprehensively examined the association between CD44 rs187115 variant and cancer risk (breast cancer, cervical cancer, lung cancer, gastric cancer, liver cancer, colon cancer, and rectal cancer) in a central Chinese population. The rs187115 variant was genotyped with the polymerase chain reaction-restriction fragment length polymorphism assay. In this study, we observed that rs187115 was associated with the risk of cervical, lung, and liver cancer, but not with the risk of breast, gastric, colon, rectal or colorectal cancer. Of note, the G allele and G allele genotypes of rs187115 conferred an increased risk of cervical, lung, and liver cancer. To improve the statistical strength, a followed meta-analysis was conducted. The results demonstrated that rs187115 was significantly associated with cancer risk, and the significant association remained in the stratification analysis by ethnicity, genotyping method, and cancer type. Collectively, the CD44 rs187115 variant may be associated with the risk of cervical, lung, and liver cancer in the central Chinese population, and may be used as a potential biomarker for cancer predisposition in the Asian population, especially in the Chinese population., (© 2019 Wiley Periodicals, Inc.)