Rong Shi

Risk of Obstructive Sleep Apnea in Parkinson’s Disease: A Meta-Analysis

Study Objectives Sleep disorders are a common symptom of Parkinson’s disease (PD) and they significantly impair the sleep quality of the PD patients. However, there is no conclusive evidence to support the relation between PD and the prevalence of obstructive sleep apnea (OSA). The purpose of this meta-analysis review is to evaluate the association between PD and the prevalence of OSA. Methods A comprehensive literature search was conducted on PubMed and Embase through July 2013. Only studies that referred to PD and the prevalence of OSA and that met the selection criteria were included in the analysis. The odds ratios (ORs) were used to evaluate the relationship of PD and the prevalence of OSA by the fixed-effect model. Results Five eligible studies were analyzed in this study including 322 cases and 6,361 controls. The pooled-analysis showed the OR to be 0.60 (95% confidence interval (CI): 0.44 to 0.81, P = 0.001) and I2 = 0.0% (χ2 = 3.90, P = 0.420) in the fixed-effect model. Conclusions Although we only included five small sample studies that indicated high homogeneity in the heterogeneity test, the results suggest that there is a significant negative association between PD and the prevalence of OSA; PD patients generally have a reduced prevalence of OSA. According to our analysis, these results are primarily due to the lower BMI of PD patients when compared with the general population controls.

Reduced expression of PinX1 correlates to progressive features in patients with prostate cancer

BackgroundPin2/TRF1 binding protein X1 (PinX1) has been identified as an endogenous telomerase inhibitor and a major haploinsufficient tumor suppressor gene. Increasing evidence suggests that reduced expression of PinX1 plays a key role in tumorigenesis. However, the PinX1 expression status and its correlation with the clinicopathological features in prostate cancer (PCa) have not been investigated.MethodsPinX1 mRNA and protein expression in PCa and adjacent normal prostate tissues were evaluated by real-time quantitative RT-PCR (qRT-PCR) and western blotting. The clinicopathological significance of PinX1 was investigated by immunohistochemistry (IHC) analysis on a PCa tissue microarray (TMA). The cut-off score for positive expression of PinX1 was determined by the receiver operating characteristic (ROC) analysis. The correlation between PinX1 expression and clinicopathological features of PCa was analyzed by Chi-square test.ResultsReduced expression of PinX1 mRNA and protein was observed in the majority of PCa, compared with their paired adjacent normal prostate tissues. When PinX1 positive expression percentage was determined to be above 60% (area under ROC curve = 0.833, P = 0.000), positive expression of PinX1 was observed in 100% (8/8) of normal prostate tissues and 32.5% (13/40) of PCa tissues by IHC. Reduced expression of PinX1 in patients was correlated with advanced clinical stage (χ2 = 10.230, p = 0.017), high Gleason score (χ2 = 4.019, p = 0.045), positive regional lymph node metastasis (χ2 = 10.852, p = 0.004) and distant metastasis (χ2 = 7.965, p = 0.005).ConclusionsOur findings suggest that reduced expression of PinX1 is correlates to progressive features in patients with PCa and may serve as a potential marker for diagnosis.

The association between two polymorphisms in the TS gene and risk of cancer: A systematic review and pooled analysis

Thymidylate synthase (TS) is an important enzyme involved in folate metabolism and catalyzes methylation of deoxyuridine monophosphate to deoxythymidine monophosphate, which is essential for DNA replication. Thymidylate synthase enhancer region (TSER) and TS1494del6, two functionally important and ethnically diverse polymorphisms mapping to its gene region, are the most extensively studied. Considering the potential influence of altering TS activity, it is plausible that TS polymorphisms might play a role in the development of cancer. Although the effects of TS polymorphisms on susceptibility to human cancer have been investigated in many studies, the results remain conflicting rather than conclusive. To resolve these conflicts, we performed a quantitative synthesis of the evidence on the association between these two polymorphisms and cancer risk, including 63 studies (19,707 cases and 27,398 controls) for TSER polymorphism and 39 studies (13,489 cases and 16,297 controls) for TS1494del6 polymorphism. Our meta‐analysis suggested that these two polymorphisms are not associated with cancer risk when all studies were pooled together. In the stratified analyses, we found that individuals with 2R/2R genotype had a significantly higher cancer risks among Asians (2R/2R vs. 3R/3R: odds ratio [OR] = 1.24, 95% confidence interval (95% CI) = 1.05–1.45; recessive model: OR = 1.23, 95% CI = 1.05–1.44). Further analyses revealed that 2R/2R genotype was significantly associated with an increased risk of gastroesophageal cancer among Asians, whereas it might provide protecting effects against colorectal cancer risk in a dominant genetic model for Caucasians. Additionally, TS1494del6 polymorphism may contribute to genetic susceptibility of breast cancer among Asians.

MiR-204-5p/Six1 feedback loop promotes epithelial-mesenchymal transition in breast cancer.

Epithelial–mesenchymal transition (EMT) is a vital process in epithelial cancer invasion and metastasis. The induction of EMT by Six1 has been described as a common mode of cancer progression, which could promote breast cancer migration and invasion. In the study, we found that miR-204-5p could suppress the migration and invasion of breast cancer cell lines. Since overexpression of Six1 promote EMT, we identified a mechanism by which miR-204-5p inhibited the EMT by downregulating the Six1, which was mediated by a conserved miR-204-5p seed-matching sequence in the 3′-UTR of Six1 mRNA. We also identified that upregulation of Six1 could downregulate miR-204-5p expression, affecting the migration and invasion of breast cancer cell lines. In conclusion, the frequent upregulation of Six1 and/or downregulation of miR-204-5p in breast cancer may shift the equilibrium of these reciprocal regulations and lock breast cancer cells in the mesenchymal state.

MiR-519d facilitates the progression and metastasis of cervical cancer through direct targeting Smad7

BackgroundMicroRNAs (miRNAs) play pivotal roles in the development of various cancer types, including cervical cancer.Methods and resultsIn this study, we showed that miR-519d, a miRNA within the chromosome 19 miRNA cluster, was significantly upregulated in cervical cancer tissues, compared with non-tumorous cervical samples. Suppression of miR-519d markedly attenuated the migration and invasion of HeLa and SiHa cervical cancer cells. Additionally, miR-519d inhibited the apoptosis of cervical cancer cells, and the proliferation of cervical cancer cells was also affected following transfection of miR-519d inhibitor. Moreover, we identified Smad7 to be a novel target of miR-519d in cervical cancer cells. MiR-519d matched the 3′-UTR of Smad7 mRNA. Transfection with miR-519d mimics led to apparent downregulation of Smad7 both at the mRNA and protein levels. Luciferase reporter analysis revealed that miR-519d reduced the luciferase activity of Smad7 mRNA 3′-UTR through matching site-dependent manner. And more notably, suppression of Smad7 remarkably restored the migration and invasion of miR-519d-depleted cervical cancer cells.ConclusionTaken together, these findings implicated that miR-519d promoted the progression and metastasis of cervical cancer through targeting Smad7.

XRCC1 gene polymorphisms and glioma risk in Chinese population: a meta-analysis.

Background Three extensively investigated polymorphisms (Arg399Gln, Arg194Trp, and Arg280His) in the X-ray repair cross-complementing group 1 (XRCC1) gene have been implicated in risk for glioma. However, the results from different studies remain inconsistent. To clarify these conflicts, we performed a quantitative synthesis of the evidence to elucidate these associations in the Chinese population. Methods Data were extracted from PubMed and EMBASE, with the last search up to August 21, 2014. Meta-analysis was performed by critically reviewing 8 studies for Arg399Gln (3062 cases and 3362 controls), 8 studies for Arg194Trp (3419 cases and 3680 controls), and 5 studies for Arg280His (2234 cases and 2380 controls). All of the statistical analyses were performed using the software program, STATA (version 11.0). Results Our analysis suggested that both Arg399Gln and Arg194Trp polymorphisms were significantly associated with increased risk of glioma (for Arg399Gln polymorphism: Gln/Gln vs. Arg/Arg, OR = 1.82, 95% CI = 1.46–2.27, P = 0.000; Arg/Gln vs. Arg/Arg, OR = 1.25, 95% CI = 1.10–1.42, P = 0.001 and for Arg194Trp polymorphism: recessive model, OR = 1.78, 95% CI = 1.44–2.19, P = 0.000), whereas the Arg280His polymorphism had no influence on the susceptibility to glioma in a Chinese population. Conclusions This meta-analysis suggests that there may be no association between the Arg280His polymorphism and glioma risk, whereas the Arg399Gln/Arg194Trp polymorphisms may contribute to genetic susceptibility to glioma in the Chinese population. Nevertheless, large-scale, well-designed and population-based studies are needed to further evaluate gene-gene and gene–environment interactions, as well as to measure the combined effects of these XRCC1 variants on glioma risk.

The Role of PinX1 in Growth Control of Breast Cancer Cells and Its Potential Molecular Mechanism by mRNA and lncRNA Expression Profiles Screening

As a major tumor suppressor gene, the role of PinX1 in breast cancer and its molecular mechanism remain unclear. In this study, overexpression of PinX1 was generated in 3 breast cancer cell lines, and knockdown of PinX1 was performed in a nontumorigenic breast cell line. The regulation of PinX1 on cell proliferation and cell cycle was observed. A microarray-based lncRNA and mRNA expression profile screening was also performed. We found a lower growth rate, G0/G1 phase arrest, and S phase inhibition in the PinX1 overexpressed breast cancer cells, while a higher growth rate, decreased G0/G1 phase, and increased S phase rate in the PinX1 knocked-down nontumorigenic breast cell. A total of 977 mRNAs and 631 lncRNAs were identified as differentially expressed transcripts between PinX1 overexpressed and control MCF-7 cells. Further analysis identified the involvement of these mRNAs in 52 cancer related pathways and various other biological processes. 11 enhancer-like lncRNAs and 25 lincRNAs with their adjacent mRNA pairs were identified as coregulated transcripts. Our results confirmed the role of PinX1 as a major tumor suppressor gene in breast cancer cell lines and provided information for further research on the molecular mechanisms of PinX1 in tumorigenesis.

An Activated GOPS-poly-L-Lysine- Coated Glass Surface for the Immobilization of 60mer Oligonucleotides

To explore a method for enhancing the immobilization and hybridization efficiency of oligonucleotides on DNA microarrays, conventional protocols of poly‐L‐lysine coating were modified by means of surface chemistry, namely, the slides were prepared by the covalently coupling of poly‐L‐lysine to a glycidoxy‐modified glass surface. The modified slides were then used to print microarrays for the detection of the SARS coronavirus by means of 60mer oligonucleotide probes. The characteristics of the modified slides concerning immobilization efficiency, hybridization dynamics, and probe stripping cycles were determined. The improved surface exhibited high immobilization efficiency, a good quality uniformity, and satisfactory hybridization dynamics. The spotting concentration of 10 μmol/L can meet the requirements of detection; the spots were approximately 170 nm in diameter; the mean fluorescence intensity of the SARS spots were between 3.2 × 104 and 5.0 × 104 after hybridization. Furthermore, the microarrays prepared by this method demonstrated more resistance to consecutive probe stripping cycles. The activated GOPS‐PLL slide could undergo hybridization stripping cycles for at least three cycles, and the highest loss in fluorescence intensity was found to be only 11.9 % after the third hybridization. The modified slides using the above‐mentioned method were superior to those slides treated with conventional approaches, which theoretically agrees with the fact that modification by surface chemistry attaches the DNA covalently firmly to the slides. This protocol may have great promise in the future for application in large‐scale manufacture.

The expression and clinical significance of HERC4 in breast cancer

BackgroundIncreasing evidence suggest that ubiquitin-proteasome system (UPS) plays a key role in tumorigenesis. HERC4 is a recently identified ubiqutin ligase. However, the expression status and biological functions of HERC4 in cancers are not clearly.MethodsWe evaluated the HERC4 expression in breast cancer cell lines and breast tumor tissues by quantitative real-time PCR and western blot analysis. To investigate the clinicopathological significance of HERC4, immunohistochemistry analysis for HERC4 was performed on a tissue microarray including 13 benign fibroadenoma, 15 intraductal carcinoma, 120 histologically confirmed invasive ductal carcinoma. Receiver operating characteristic (ROC) analysis was applied to determine the optimal cut-off score for positive expression of HERC4, when HERC4 positive expression percentage was above 60%, tumor was defined as “positive”.ResultsHERC4 was up-regulated in breast cancer cell lines and breast tumor tissues compared to non-tumorigenic cell line and adjacent normal breast tissues. According to ROC analysis, HERC4 positive expression was detected in 1/16 (6.3%) of normal breast tissue, in 3/13 (23.1%) of fibroadenoma, in 6/15 (40%) of intraductal carcinoma and 66/120 (55%) of invasive ductal carcinoma. Positive expression of HERC4 was positively correlated with pT status, pN status, clinical stage and histological grade of patients with invasive ductal carcinoma (p < 0.05).ConclusionsOur findings suggest that HERC4 was a significant diagnostic marker for invasive ductal carcinoma of the breast.

Association between APE1 Asp148Glu polymorphism and the risk of urinary cancers: a meta-analysis of 18 case–control studies

Background Several observational studies suggested that APE1 Asp148Glu was significantly associated with urinary cancers; however, the results of published studies are inconsistent. Materials and methods The PubMed and EMBASE were searched for case–control studies regarding the association between Asp148Glu and the risk of urinary cancers with a time limit of September 12, 2015. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association between Asp148Glu and the risk of developing prostate cancer, kidney cancer, bladder cancer, as well as all urinary cancers combined. Results A total of 18 case–control studies were included in the analysis. Our meta-analysis revealed that the inheritance of at least one APE1 148Glu among Asian men was associated with a 1.26-fold increase in the risk of developing urinary cancers. Meanwhile, APE1 Asp148Glu was significantly associated with the risk of prostate cancer. However, there were no significant relationships between the APE1 SNP (single nucleotide polymorphism) and all urinary cancers combined and bladder cancer and kidney cancer among the men of Caucasian/Asian/African descent or all racial/ethnic groups combined. When stratified by the quality score, no significant association was found in high-quality studies (score ≥7), but a significant increased risk of urinary cancers was observed in lower quality studies (score <7) (dominant model: OR=1.27, 95% CI=1.11–1.45). Conclusion Our meta-analysis suggests that APE1 Asp148Glu was not associated with the risk of urinary cancers but might increase the risk of urinary cancers among Asians. Stratification by cancer type identified a significant association of Asp148Glu with prostate cancer.