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The progression of prostate cancer (PCa) leads to poor prognosis. However, the molecular mechanism of PCa is still not completely clear. This study aimed to elucidate the important role of centromere protein A (CENPA) in PCa. Large numbers of bulk RNA sequencing (RNA‐seq) data and in‐house immunohistochemistry data were used in analysing the expression level of CENPA in PCa and metastatic PCa (MPCa). Single‐cell RNA‐seq data was used to explore the expression status of CENPA in different prostate subpopulations. Enrichment analysis was employed to detect the function of CENPA in PCa. Clinicopathological parameters analysis was utilised in analysing the clinical value of CENPA. The results showed that CENPA was upregulated in PCa (standardised mean difference [SMD] = 0.83, p = 0.001) and MPCa (SMD = 0.61, p = 0.029). CENPA was overexpressed in prostate cancer stem cells (CSCs) with androgen receptor (AR) negative compared to epithelial cells with AR positive. CENPA may influence the development of PCa through affecting cell cycle. Patients with nodal metastasis had higher expression level of CENPA. And patients with high CENPA expression had poor disease‐free survival. Taken together, Overexpression of CENPA may influence the development of PCa by regulating cell cycle and promoting metastasis. [ABSTRACT FROM AUTHOR]

Background: Brain-derived neurotrophic factor (BDNF) has been implicated in cognitive performance and the modulation of several metabolic parameters in some disease models, but its potential roles in successful aging remain unclear. We herein sought to define the putative correlation between BDNF Val66Met and several metabolic risk factors including BMI, blood pressure, fasting plasma glucose (FPG) and lipid levels in a long-lived population inhabiting Hongshui River Basin in Guangxi.Methods: BDNF Val66Met was typed by ARMS-PCR for 487 Zhuang long-lived individuals (age ≥ 90, long-lived group, LG), 593 of their offspring (age 60-77, offspring group, OG) and 582 ethnic-matched healthy controls (aged 60-75, control group, CG) from Hongshui River Basin. The correlations of genotypes with metabolic risks were then determined.Results: As a result, no statistical difference was observed on the distribution of allelic and genotypic frequencies of BDNF Val66Met among the three groups (all P > 0.05) except that AA genotype was dramatically higher in females than in males of CG. The HDL-C level of A allele (GA/AA genotype) carriers was profoundly lower than was non-A (GG genotype) carriers in the total population and the CG (P = 0.009 and 0.006, respectively), which maintained in females, hyperglycemic and normolipidemic subgroup of CG after stratification by gender, BMI, glucose and lipid status. Furthermore, allele A carriers, with a higher systolic blood pressure, exhibited 1.63 folds higher risk than non-A carriers to be overweight in CG (OR = 1.63, 95% CI: 1.05 - 2.55, P = 0.012). Multiple regression analysis displayed that the TC level of LG reversely associated with BDNF Val66Met genotype.Conclusions: These data suggested that BDNF 66Met may play unfavorable roles in blood pressure and lipid profiles in the general population in Hongshui River area which might in part underscore their poorer survivorship versus the successful aging individuals and their offspring. [ABSTRACT FROM AUTHOR]

Little is known about the association between the single nucleotide polymorphisms ( SNPs) and haplotypes of the dedicator of cytokinesis 7 ( DOCK7), pro-protein convertase subtilisin/kexin type 9 ( PCSK9) and polypeptide N-acetylgalactosaminyltransferase 2 ( GALNT2) and serum lipid traits in the Chinese populations. This study was to determine the association between nine SNPs in the three genes and their haplotypes and hypercholesterolaemia ( HCH)/hypertriglyceridaemia ( HTG), and to identify the possible gene-gene interactions among these SNPs. Genotyping was performed in 733 HCH and 540 HTG participants. The haplotype of C-C-G-C-T-G-C-C-G [in the order of DOCK7 rs1168013 (G>C), rs10889332 (C>T); PCSK9 rs615563 (G>A), rs7552841 (C>T), rs11206517 (T>G); and GALNT2 rs1997947 (G>A), rs2760537 (C>T), rs4846913 (C>A) and rs11122316 (G>A) SNPs] was associated with increased risk of HCH and HTG. The haplotypes of C-C-G-C-T-G-C-C-A and G-C-G-T-T-G-T-C-G were associated with a reduced risk of HCH and HTG. The haplotypes of G-C-G-C-T-G-C-C-A and G-C-G-C-T-G-T-C-G were associated with increased risk of HCH. The haplotypes of C-T-G-C-T-G-C-C-G, G-C-A-C-T-G-C-C-G and G-C-G-C-T-G-C-C-A were associated with an increased risk of HTG. The haplotypes of G-C-G-C-T-G-T-C-A and G-C-G-T-T-G-T-C-G were associated with a reduced risk of HTG. In addition, possible inter-locus interactions among the DOCK7, PCSK9 and GALNT2 SNPs were also noted. However, further functional studies of these genes are still required to clarify which SNPs are functional and how these genes actually affect the serum lipid levels. [ABSTRACT FROM AUTHOR]

Background: Maonan nationality belongs to a mountain ethnic minority in China. Little is known about the association of apolipoprotein A1 gene (APOA1) rs964184 single nucleotide polymorphism (SNP) and serum lipid levels in this population. The aim of this study was to detect the association of the APOA1 rs964184 SNP and several environmental factors with serum lipid profiles in the Chinese Maonan and Han populations. Methods: Genotypes of the APOA1 rs964184 SNP in 867 individuals of Maonan nationality and 820 participants of Han nationality were determined by polymerase chain reaction and restriction fragment length polymorphism, combined with gel electrophoresis, and confirmed by direct sequencing. Results: The frequencies of CC, CG and GG genotypes of the APOA1 rs964184 SNP were 68.86, 29.18 and 1.96% in the Maonan population, and 63.78, 30.85 and 5.37% in the Han population (P < 0.001). The frequency of the G allele was 16.55% in Maonan and 20.79% in Han (P < 0.001). The G allele carriers had lower high-density lipoprotein cholesterol (HDL-C) levels in Maonan and higher triglyceride (TG) levels in Han peoples than the G allele non-carriers. Subgroup analyses showed that the G allele carriers had lower HDL-C levels in both Maonan males and females; and lower apolipoprotein (Apo) A1 levels and the ApoA1/ApoB ratio in Han males than the G allele non-carriers. Serum lipid parameters in the two ethnic groups were also associated with several environmental factors. Conclusions: The present study reveals that there may be a racial/ethnic- and/or gender-specific association between the APOA1 rs964184 SNP and serum lipid parameters in our study populations. Trial registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background and Aim: Extensive research has revealed that microRNAs (miRNAs) play a principle role in cancer, and miRNAs associated with specific cancers have also been identified. The role of microRNA (miR)-302b-5p, which is one of the miRNAs reported in association with cancer, in hepatocellular carcinoma (HCC) is still unclear. Thus, the present study aimed to reveal the expression and potential molecule mechanism of miR-302b-5p in HCC., Methods: An extensive meta-analysis of data from real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR), Gene Expression Omnibus and ArrayExpress microarrays was used to determine the expression of miR-302b-5p in HCC tissue samples and non-cancerous liver tissue samples. The sensitivity and specificity of miR-302b-5p as an indicator of HCC was estimated by plotting the receiver operating characteristic (ROC) and summarized ROC (sROC). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were employed to unravel the molecular mechanisms and biological functions of miR-302b-5p in HCC. Further, the putative target genes of miR-302b-5p were harvested based on the predicted genes and differentially expressed genes in HCC. Finally, the protein-protein interaction (PPI) network was built to determine the hub genes., Results: According to the RT-qPCR results, the expression of miR-302b-5p was pronouncedly decreased in 39 HCC tissue samples as compared to 39 non-cancerous liver tissue samples. The standard mean difference (SMD) values of all the samples used in the meta-analysis also indicated lower miR-302b-5p expression in the 558 HCC tissue samples than in the 286 non-cancerous liver tissue samples. ROC and sROC analyses showed that miR-302b-5p had good specificity and sensitivity for distinguishing HCC tissue from non-cancerous liver tissue. Bioinformatics analyses identified 227 putative genes, and these genes were evidently enriched in the processes of organelle fission, chromosome and chromatin binding and were centralized in a "lysosome" pathway. The PPI network indicated that DNA topoisomerase II alpha (TOP2 A) was the most prominent hub gene of miR-302b-5p in HCC. Interestingly, according to the TCGA and Genotype-Tissue Expression databases, the mRNA and protein expression of TOP2 A were both elevated in HCC tissue samples as compared to non-cancerous liver tissue samples, and the overall survival and disease-free survival revealed that a high level of TOP2 A might reflect poor HCC outcome., Conclusions: Our findings indicate that miR-302b-5p might suppress HCC progression, and TOP2 A might be a potential target of miR-302b-5p in HCC. However, in-depth in vivo and in vitro experiments are required to verify these findings and explore the mechanisms involved., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Background: The miR-191-5p expression has been reported to increase in hepatocellular carcinoma (HCC), but its clinical value and exact role remain to be further clarified. Thus, a comprehensive analysis was performed in the current study to explore the underlying function of miR-191-5p in HCC., Methods: HCC-related expression data were collected to conduct a thorough analysis to determine the miR-191-5p expression and its clinical significance in HCC, including microarray data from the Gene Expression Omnibus and ArrayExpress database as well as quantitative real-time polymerase chain reaction (qRT-PCR) data of 178 matched clinical samples. The underlying relationship between miR-191-5p and HCC was also explored on the basis of a series of bioinformatics analyses., Results: The overall pooled meta-analysis showed an overexpression of miR-191-5p in the HCC samples (SMD=0.400, 95% CI=0.139-0.663, P=0.003), consistent with the detected result of the clinical HCC samples through the qRT-PCR analysis. Higher miR-191-5p levels were correlated with advanced TNM stages (III and IV), higher pathological grades, and metastasis. Functionally, 64 potential target genes were acquired for further mechanism analysis. Two pathways (p75 neurotrophin receptor and liver kinase B1-mediated signaling pathways), which were likely modulated by miR-191-5p, were regarded to be linked to the deterioration of HCC. Early growth response 1 and UBE2D3 were identified as the most likely targets for miR-191-5p in HCC and were commonly implied in the top enriched pathways and protein-protein network., Conclusions: In summary, miR-191-5p may function as a tumor promoter miRNA of HCC, and the miR-191-5p inhibitor may contribute to the targeted HCC treatment in the future., Competing Interests: None., (IJCEP Copyright © 2019.)

The correlation between the BDNF rs11030104 single nucleotide polymorphism (SNP) and serum lipid levels has been understudied. The present study was conducted to detect the association of the BDNF rs11030104 SNP and several environmental factors with serum lipid levels in the Jing and Han nationalities. Genotypes of the BDNF rs11030104 SNP in 709 unrelated subjects of Han and 706 unrelated participants of Jing populations were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and further verified by direct sequencing. There was no significant difference in either genotypic or allelic frequencies between the Han and Jing populations. The genotypic and allelic frequencies of the SNP in Jing but not in Han populations were different between male and female subgroups ( P <0.05 for each). The levels of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the Jing population were different among the genotypes, the G allele carriers had lower TC and LDL-C levels than the G allele non-carriers. Subgroup analyses showed that the differences in serum TC and LDL-C levels among the genotypes were observed in the Jing males but not in females. Serum lipid profiles were also significantly associated with some environmental factors in the Han and Jing populations, or in male and female subgroups of the two ethnic groups ( P <0.05 for all). Our study exhibited a correlation between the BDNF rs11030104 SNP and serum TC and LDL-C levels in the Jing males. These results indicate that there may be a racial/ethnic- and/or sex-specific association of the BDNF rs11030104 SNP and serum lipid parameters., Competing Interests: None., (IJCEP Copyright © 2018.)

Jing nationality is a relatively conservative and isolated minority in China. Little is known about the association of the PIN2/TERF1-interacting telomerase inhibitor 1 ( PINX1 ) and N-acetyltransferase 2 ( NAT2 ) single nucleotide polymorphisms (SNPs) and serum lipid levels in the Chinese populations. This study aimed to clarify the association of 6 SNPs of the PINX1 and NAT2 and serum lipid levels in two Chinese populations. Genotyping of the SNPs was performed in 1236 Han subjects and 1248 Jing participants. Allelic and genotypic frequencies of these variants (except NAT2 rs1799931) were different between the two ethnic groups. The minor allele carriers had higher triglyceride (TG, rs11776767, rs1495743 and rs1799930), low-density lipoprotein cholesterol (rs6601530) levels and the apolipoprotein (Apo)A1/ApoB ratio (rs1495743) in Han nationality; and higher total cholesterol (rs1961456), TG (rs11776767, rs6601530 and rs1495743) and lower ApoA1 (rs6601530 and rs1799931) levels in Jing minority than the minor allele non-carriers. The SNPs were not statistically independent by the multiple-locus linkage disequilibrium analyses. The integrative haplotypes and gene-by-gene (G × G) interactions on serum lipid traits were also observed in the two populations. Association analysis based on haplotypes and G × G interactions might be powerful than single-locus tests. Differences in serum lipid profiles between the two populations might partially be attributed to these SNPs, their haplotypes and G × G interactions., Competing Interests: CONFLICTS OF INTEREST The authors have no potential conflicts of interest to report.

Maonan ethnic group is a relatively conservative and isolated minority in China. Little is known about the association of the mevalonate kinase ( MVK ), methylmalonic aciduria (cobalamin deficiency) cblB type ( MMAB ) single nucleotide polymorphisms (SNPs) and serum lipid levels. This study aimed to determine the association between four SNPs in the MVK/MMAB and serum lipid levels. Genotyping of the rs3759387, rs877710, rs7134594 and rs9593 SNPs was performed in 1264 Maonan subjects and 1251 Han participants. Allele and genotype frequencies of the selected SNPs were different between the two populations ( P < 0.05-0.001). Four SNPs were associated with high-density lipoprotein cholesterol (HDL-C) in the both ethnic groups ( P < 0.0125-0.001); and one SNP with apolipoprotein (Apo) A1 (rs7134594) in Han Chinese ( P < 0.0125). Strong linkage disequilibria were noted among the SNPs ( D '=0.63-0.96; r 2 =0.13-0.88). The commonest haplotype was C-C-C-T (> 50%). The frequencies of C-C-C-T, C-G-T-A, A-G-T-A, C-G-C-T, and A-C-T-A were different between the two populations ( P < 0.001). The associations between haplotypes and dyslipidemia were different in the Han and/or Maonan population ( P < 0.05-0.001), haplotypes could explain much more serum lipid variation than any single SNP alone especially for HDL-C. Differences in lipid profiles between the two populations might partially attribute to these SNPs and their haplotypes., Competing Interests: CONFLICTS OF INTEREST The authors have no potential conflicts of interest to report.

To see the possible relationship between COMT Val158Met polymorphism and blood pressure (BP) and serum lipid levels and its putative role in human longevity, we genotyped COMT Val158Met (rs4680) by PCR-RFLP for members from Bama long-lived families (BLF, n = 1538), Bama non-long-lived families (BNLF, n = 600), Pingguo (a county outside Bama region) long-lived families (PLF, n = 538) and Pingguo non-long-lived families (PNLF, n = 403) after anthropometric measures were collected and serum lipid levels were detected. The distribution of genotypes and alleles among four family groups was significantly different (all P < 0.01), with GA/AA genotype and minor allele A presenting more frequently in Bama population than Pingguo Population (P < 0.01). The systolic blood pressure (SBP), pulse pressure (PP), total cholesterol (TC), triglyceride (TG) and low density lipoprotein-cholesterol (LDL-C) levels of GG genotype carriers were dramatically higher than non-GG carriers in BNLF (P < 0.05); the SBP and PP levels of GG carriers were lower (P < 0.05) while TC, LDL-C level were higher (P < 0.01) than that of non-GG carriers in PLF; no difference in blood pressure and lipids were observed between genotypes in BLF and PNLF (P > 0.05). Correlation analyses revealed that COMT Val158Met was mainly correlated negatively with SBP, diastolic blood pressure (DBP) and LDL-C in BNLF and negatively with TC level in BLF, BNLF and PLF. These data suggest that COMT Val158Met polymorphism may have more impact on the modulation of BP and lipid profiles in the average families than in the long-lived families in Bama region. The association between this SNP and other phenotypes (e.g. cognition) and its roles in the longevity in Bama area thus warrant further investigation.

Both Jing and Mulao nationalities are the isolated minorities in China. Little is known about the prevalence of dyslipidemia between the two ethnic groups. Therefore, the aim of this study was to compare the differences in serum lipid profiles, the prevalence of dyslipidemia and their risk factors between the Jing and Mulao populations. A cross-sectional study of dyslipidemia was conducted in Dongxing city, Guangxi, China, during Dec 2011 and Jan 2012. A total of 1254 subjects of Jing and 1251 participants of Mulao were surveyed by a stratified randomized sampling. Information on demography, diet and lifestyle was collected with standardized questionnaire. Serum lipid levels were detected using the commercially available kits. The levels of low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) A1, and the ratio of ApoA1 to ApoB were lower but the levels of ApoB were higher in Jing than in Mulao (P < 0.001 for all). The prevalence of hypertriglyceridemia (32.38% vs. 24.38%), high ApoB (35.25% vs. 15.35%) and low ApoA1/ApoB ratio (22.65% vs. 16.87%) was higher and low high-density lipoprotein cholesterol (0.48% vs. 2.16%), high LDL-C (17.54% vs. 40.53%) and low ApoA1 (5.98% vs. 11.43%) was lower in Jing than in Mulao (P < 0.001 for all). The risk factors for serum lipid parameters and hyperlipidemia were different between the two ethnic groups. Serum lipid profiles, the prevalence of dyslipidemia and their risk factors are different between the Jing and Mulao populations. These differences may result from the combined effects of different diet, lifestyle, and genetic factors.

The association of ADP-ribosylation factor-like 15 (ARL15) rs6450176 single nucleotide polymorphism (SNP) and serum lipid profiles has never been studied in the Chinese population. The present study was undertaken to detect the association of ARL15 rs6450176 SNP and several environmental factors with serum lipid levels in the Jing and Han populations. Genotypes of the SNP were determined in 726 unrelated subjects of Jing nationality and 726 participants of Han nationality. The genotypic and allelic frequencies of the SNP in Jing but not in Han were different between males and females (P < 0.001 and P < 0.05; respectively). The G allele carriers in Han had lower serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) B levels, and higher ApoA1/ApoB ratio than the G allele non-carriers (P < 0.05-0.01). The G allele carriers in Jing had lower serum TC, high-density lipoprotein cholesterol (HDL-C), ApoA1, ApoB levels and higher ApoA1/ApoB ratio than the G allele non-carriers (P < 0.05 for all). Subgroup analyses showed that the G allele carriers had lower TC and LDL-C levels in Han males; lower LDL-C and ApoB levels in Han females; lower ApoB levels and ApoA1/ApoB ratio in Jing males; and lower LDL-C levels in Jing females than the G allele non-carriers (P < 0.05-0.01). Multiple linear regression analysis showed that serum TC, LDL-C, ApoB levels and the ApoA1/ApoB ratio in Han; and TC, HDL-C and ApoA1 levels in Jing were correlated with the genotypes of the ARL15 rs6450176 SNP (P < 0.05-0.001). Serum lipid parameters were also associated with several environmental factors in both ethnic groups. These findings indicated that there may be a racial/ethnic- and/or sex-specific association of the ARL15 rs6450176 SNP and serum lipid levels.

SPT2 chromatin protein domain containing 1 gene (SPTY2D1) is a candidate gene for dyslipidemia. The single nucleotide polymorphism (SNP) of rs7934205 near SPTY2D1 locus was ethnic- and sex-specific associated with serum lipid levels in our previous study. Whether SPTY2D1 rs17579600 SNP and several environmental factors are associated with serum lipid profiles is unknown. A total of 712 participants of Han and 689 unrelated individuals of Mulao were included. The genotype and allele frequencies of SPTY2D1 rs17579600 SNP were different between the Han and Mulao populations (TT, 74.3% vs. 55.7%; TC, 17.6% vs. 31.2%, CC, 8.1% vs. 13.1%, P = 0.028; T, 83.1% vs. 71.3%; C, 16.9% vs. 28.7%, P = 0.044), and between males and females in the both ethnic groups. The levels of serum apolipoprotein (Apo) A1 in Han, triglyceride (TG) in Mulao, and total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), ApoA1 and ApoB in Mulao males were difference among the genotypes. The C allele carriers had higher ApoA1 in Han, lower TG in Mulao, and lower TC, LDL-C and ApoB and higher ApoA1 in Mulao males than the C allele non-carriers. Serum lipid parameters were also associated with several environmental factors in both ethnic groups. The differences suggesting there may be a racial/ethnic- and/or sex-specific association between the SPTY2D1 rs17579600 SNP and serum lipid parameters in some ethnic groups.