16 results on '"Zhao-Qian Liu"'
Search Results
2. Genome-scale analysis identifies NEK2, DLGAP5 and ECT2 as promising diagnostic and prognostic biomarkers in human lung cancer
- Author
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Yuan-Xiang Shi, Ji-Ye Yin, Yao Shen, Wei Zhang, Hong-Hao Zhou, and Zhao-Qian Liu
- Subjects
Medicine ,Science - Abstract
Abstract This study aims to identify promising biomarkers for the early detection of lung cancer and evaluate the prognosis of lung cancer patients. Genome-wide mRNA expression data obtained from the Gene Expression Omnibus (GSE19188, GSE18842 and GSE40791), including 231 primary tumor samples and 210 normal samples, were used to discover differentially expressed genes (DEGs). NEK2, DLGAP5 and ECT2 were found to be highly expressed in tumor samples. These results were experimentally confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The elevated expression of the three candidate genes was also validated using the Cancer Genome Atlas (TCGA) datasets, which consist of 349 tumor and 58 normal tissues. Furthermore, we performed receiver operating characteristics (ROC) analysis to assess the diagnostic value of these lung cancer biomarkers, and the results suggested that NEK2, DLGAP5 and ECT2 expression levels could robustly distinguish lung cancer patients from normal subjects. Finally, Kaplan-Meier analysis revealed that elevated NEK2, DLGAP5 and ECT2 expression was negatively correlated with both overall survival (OS) and relapse-free survival (RFS). Taken together, these findings indicate that these three genes might be used as promising biomarkers for the early detection of lung cancer, as well as predicting the prognosis of lung cancer patients.
- Published
- 2017
- Full Text
- View/download PDF
3. Effect of carboxylesterase 1 S75N on clopidogrel therapy among acute coronary syndrome patients
- Author
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Fei-Yan Xiao, Jian-Quan Luo, Min Liu, Bi-Lian Chen, Shan Cao, Zhao-Qian Liu, Hong-Hao Zhou, Gan Zhou, and Wei Zhang
- Subjects
Medicine ,Science - Abstract
Abstract Carboxylesterase 1 (CES1) hydrolyzes the prodrug clopidogrel to an inactive carboxylic acid metabolite. The effects of CES1 S75N (rs2307240,C>T) on clopidogrel response among 851 acute coronary syndrome patients who came from the north, central and south of China were studied. The occurrence ratios of each endpoint in the CC group were significantly higher than in the CT + TT group for cerebrovascular events (14% vs 4.8%, p
- Published
- 2017
- Full Text
- View/download PDF
4. Gene-gene and gene-environment interactions influence platinum-based chemotherapy response and toxicity in non-small cell lung cancer patients
- Author
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Jia-Jia Cui, Lei-Yun Wang, Tao Zhu, Wei-Jing Gong, Hong-Hao Zhou, Zhao-Qian Liu, and Ji-Ye Yin
- Subjects
Medicine ,Science - Abstract
Abstract Platinum-based chemotherapy is a major therapeutic regimen of lung cancer. Various single nucleotide polymorphisms (SNPs) reported were associated with platinum-based chemotherapy response and drug toxicity. However, neither of the studies explored this association from SNP-SNP interaction perspective nor taking into effects of SNP-environment consideration simultaneously. We genotyped 504 polymorphisms and explore the association of gene-gene and gene-environment interactions with platinum-based chemotherapy response and toxicity in 490 NSCLC patients. 16 SNPs were found significantly associated with platinum-based chemotherapy, and they were picked out as study object in the validation cohort. We recruited 788 patients in the validation cohort. We found that HSPD1 rs17730989-SUMF1 rs2633851 interaction was associated with platinum-based chemotherapy-induced hematologic toxicity (adjusted OR = 0.233, P = 0.018). In addition, the combined effect of ABCG2 rs2231142-CES5A rs3859104 was significantly associated with overall toxicity (adjusted OR = 8.044, P = 4.350 × 10−5). Besides, the model of ARHGAP26 rs3776332-ERCC6 rs2228528-SLC2A1 rs4658-histology was associated with platinum-based chemotherapeutic response. Gene-gene and gene-environment interactions have been identified to contribute to chemotherapy sensitivity and toxicity. They can potentially predict drug response and toxicity of platinum-based chemotherapy in NSCLC patients.
- Published
- 2017
- Full Text
- View/download PDF
5. Genetic Polymorphisms and Platinum-based Chemotherapy Treatment Outcomes in Patients with Non-Small Cell Lung Cancer: A Genetic Epidemiology Study Based Meta-analysis
- Author
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Li-Ming Tan, Cheng-Feng Qiu, Tao Zhu, Yuan-Xiang Jin, Xi Li, Ji-Ye Yin, Wei Zhang, Hong-Hao Zhou, and Zhao-Qian Liu
- Subjects
Medicine ,Science - Abstract
Abstract Data regarding genetic polymorphisms and platinum-based chemotherapy (PBC) treatment outcomes in patients with NSCLC are published at a growing pace, but the results are inconsistent. This meta-analysis integrated eligible candidate genes to better evaluate the pharmacogenetics of PBC in NSCLC patients. Relevant studies were retrieved from PubMed, Chinese National Knowledge Infrastructure and WANFANG databases. A total of 111 articles comprising 18,196 subjects were included for this study. The associations of genetic polymorphisms with treatment outcomes of PBC including overall response rate (ORR), overall survival (OS) and progression-free survival (PFS) were determined by analyzing the relative risk (RR), hazard ration (HR), corresponding 95% confidence interval (CI). Eleven polymorphisms in 9 genes, including ERCC1 rs11615 (OS), rs3212986 (ORR), XPA rs1800975 (ORR), XPD rs1052555 (OS, PFS), rs13181 (OS, PFS), XPG rs2296147 (OS), XRCC1 rs1799782 (ORR), XRCC3 rs861539 (ORR), GSTP1 rs1695 (ORR), MTHFR rs1801133 (ORR) and MDR1 rs1045642 (ORR), were found significantly associated with PBC treatment outcomes. These variants were mainly involved in DNA repair (EXCC1, XPA, XPD, XPG, XRCC1 and XRCC3), drug influx and efflux (MDR1), metabolism and detoxification (GSTP1) and DNA synthesis (MTHFR), and might be considered as potential prognostic biomarkers for assessing objective response and progression risk in NSCLC patients receiving platinum-based regimens.
- Published
- 2017
- Full Text
- View/download PDF
6. Long noncoding RNA expression signature to predict platinum-based chemotherapeutic sensitivity of ovarian cancer patients
- Author
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Rong Liu, Ying Zeng, Cheng-Fang Zhou, Ying Wang, Xi Li, Zhao-Qian Liu, Xiao-Ping Chen, Wei Zhang, and Hong-Hao Zhou
- Subjects
Medicine ,Science - Abstract
Abstract Dysregulated long noncoding RNAs (lncRNAs) are potential markers of several tumor prognoses. This study aimed to develop a lncRNA expression signature that can predict chemotherapeutic sensitivity for patients with advanced stage and high-grade serous ovarian cancer (HGS-OvCa) treated with platinum-based chemotherapy. The lncRNA expression profiles of 258 HGS-OvCa patients from The Cancer Genome Atlas were analyzed. Results revealed that an eight-lncRNA signature was significantly associated with chemosensitivity in the multivariate logistic regression model, which can accurately predict the chemosensitivity of patients [Area under curve (AUC) = 0.83]. The association of a chemosensitivity predictor with molecular subtypes indicated the excellent prognosis performance of this marker in differentiated, mesenchymal, and immunoreactive subtypes (AUC > 0.8). The significant correlation between ZFAS1 expression and chemosensitivity was confirmed in 233 HGS-OvCa patients from the Gene Expression Omnibus datasets (GSE9891, GSE63885, and GSE51373). In vitro experiments demonstrated that the ZFAS1 expression was upregulated by cisplatin in A2008, HeyA8, and HeyC2 cell lines. This finding suggested that ZFAS1 may participate in platinum resistance. Therefore, the evaluation of the eight-lncRNA signature may be clinically implicated in the selection of platinum-resistant HGS-OvCa patients. The role of ZFAS1 in platinum resistance should be further investigated.
- Published
- 2017
- Full Text
- View/download PDF
7. Author Correction: MiR-488 inhibits proliferation and cisplatin sensibility in non-small-cell lung cancer (NSCLC) cells by activating the eIF3a-mediated NER signaling pathway
- Author
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Hong-Hao Zhou, Ji-Ye Yin, Wei Zhang, Yi-Xin Chen, Zhao-Qian Liu, Hsuan-Shun Huang, Na-Yiyuan Wu, Xiang-Ping Li, and Chao Fang
- Subjects
Cisplatin ,Multidisciplinary ,business.industry ,Science ,non-small cell lung cancer (NSCLC) ,medicine.disease ,Text mining ,Cancer research ,Medicine ,Signal transduction ,business ,medicine.drug - Published
- 2021
8. Genome-scale analysis identifies NEK2, DLGAP5 and ECT2 as promising diagnostic and prognostic biomarkers in human lung cancer
- Author
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Wei Zhang, Yao Shen, Ji-Ye Yin, Hong-Hao Zhou, Yuan-Xiang Shi, and Zhao-Qian Liu
- Subjects
Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Candidate gene ,Lung Neoplasms ,Science ,Kaplan-Meier Estimate ,Bioinformatics ,Article ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,Proto-Oncogene Proteins ,Internal medicine ,Biomarkers, Tumor ,Humans ,NIMA-Related Kinases ,Medicine ,Lung cancer ,Gene ,Aged ,Multidisciplinary ,Receiver operating characteristic ,business.industry ,Human lung cancer ,Gene Expression Profiling ,Middle Aged ,Prognosis ,medicine.disease ,Primary tumor ,Neoplasm Proteins ,Gene expression profiling ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,business - Abstract
This study aims to identify promising biomarkers for the early detection of lung cancer and evaluate the prognosis of lung cancer patients. Genome-wide mRNA expression data obtained from the Gene Expression Omnibus (GSE19188, GSE18842 and GSE40791), including 231 primary tumor samples and 210 normal samples, were used to discover differentially expressed genes (DEGs). NEK2, DLGAP5 and ECT2 were found to be highly expressed in tumor samples. These results were experimentally confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The elevated expression of the three candidate genes was also validated using the Cancer Genome Atlas (TCGA) datasets, which consist of 349 tumor and 58 normal tissues. Furthermore, we performed receiver operating characteristics (ROC) analysis to assess the diagnostic value of these lung cancer biomarkers, and the results suggested that NEK2, DLGAP5 and ECT2 expression levels could robustly distinguish lung cancer patients from normal subjects. Finally, Kaplan-Meier analysis revealed that elevated NEK2, DLGAP5 and ECT2 expression was negatively correlated with both overall survival (OS) and relapse-free survival (RFS). Taken together, these findings indicate that these three genes might be used as promising biomarkers for the early detection of lung cancer, as well as predicting the prognosis of lung cancer patients.
- Published
- 2017
9. Genetic Polymorphisms and Platinum-based Chemotherapy Treatment Outcomes in Patients with Non-Small Cell Lung Cancer: A Genetic Epidemiology Study Based Meta-analysis
- Author
-
Wei Zhang, Yuan-Xiang Jin, Hong-Hao Zhou, Zhao-Qian Liu, Tao Zhu, Ji-Ye Yin, Cheng-Feng Qiu, Xi Li, and Li-Ming Tan
- Subjects
0301 basic medicine ,Oncology ,China ,medicine.medical_specialty ,Lung Neoplasms ,Science ,Antineoplastic Agents ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,XRCC1 ,0302 clinical medicine ,Asian People ,XRCC3 ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Lung cancer ,neoplasms ,Platinum ,Molecular Epidemiology ,Multidisciplinary ,biology ,Hazard ratio ,medicine.disease ,Treatment Outcome ,030104 developmental biology ,Genetic epidemiology ,Pharmacogenetics ,030220 oncology & carcinogenesis ,Methylenetetrahydrofolate reductase ,Immunology ,biology.protein ,Medicine ,ERCC1 - Abstract
Data regarding genetic polymorphisms and platinum-based chemotherapy (PBC) treatment outcomes in patients with NSCLC are published at a growing pace, but the results are inconsistent. This meta-analysis integrated eligible candidate genes to better evaluate the pharmacogenetics of PBC in NSCLC patients. Relevant studies were retrieved from PubMed, Chinese National Knowledge Infrastructure and WANFANG databases. A total of 111 articles comprising 18,196 subjects were included for this study. The associations of genetic polymorphisms with treatment outcomes of PBC including overall response rate (ORR), overall survival (OS) and progression-free survival (PFS) were determined by analyzing the relative risk (RR), hazard ration (HR), corresponding 95% confidence interval (CI). Eleven polymorphisms in 9 genes, including ERCC1 rs11615 (OS), rs3212986 (ORR), XPA rs1800975 (ORR), XPD rs1052555 (OS, PFS), rs13181 (OS, PFS), XPG rs2296147 (OS), XRCC1 rs1799782 (ORR), XRCC3 rs861539 (ORR), GSTP1 rs1695 (ORR), MTHFR rs1801133 (ORR) and MDR1 rs1045642 (ORR), were found significantly associated with PBC treatment outcomes. These variants were mainly involved in DNA repair (EXCC1, XPA, XPD, XPG, XRCC1 and XRCC3), drug influx and efflux (MDR1), metabolism and detoxification (GSTP1) and DNA synthesis (MTHFR), and might be considered as potential prognostic biomarkers for assessing objective response and progression risk in NSCLC patients receiving platinum-based regimens.
- Published
- 2017
10. Genetic polymorphisms of lncRNA-p53 regulatory network genes are associated with concurrent chemoradiotherapy toxicities and efficacy in nasopharyngeal carcinoma patients
- Author
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Yi Jin, Liang An, Wei Zhang, Zhen Guo, Hui Wang, Yu Zhao, Zhao-Qian Liu, Youhong Wang, Hong-Hao Zhou, Xiang Chen, Xiao-Ping Chen, and Bin Wu
- Subjects
0301 basic medicine ,MEG3 ,Multidisciplinary ,business.industry ,Science ,Cancer ,medicine.disease ,Bioinformatics ,03 medical and health sciences ,030104 developmental biology ,Nasopharyngeal carcinoma ,Genetic variation ,Cohort ,Genotype ,medicine ,Medicine ,Author Correction ,Adverse effect ,business ,Gene - Abstract
The relevance of the transcription factor p53 in cancer is inarguable, and numerous lncRNAs are involved in the p53 regulatory network as either regulators or effectors, triggering a transcriptional response that causes either cell arrest or apoptosis following DNA damage in a p53-dependent manner. Despite the fact that the therapeutic response is improved in NPC, heterogeneity among people remains with regard to the susceptibility of adverse effects and the efficacy of treatments. Therefore, we analysed eight potentially functional SNPs of five genes in the lncRNA-p53 regulatory network in a discovery cohort of 505 NPC patients. By performing multivariate logistic regression, the impact of genetic variations on the efficacy and risk of CRT-induced toxicities was investigated. The most dramatic finding was that the MEG3 rs10132552 CC genotype had a greater than three-fold increased risk of developing grade 3–4 anaemia (OR = 3.001, 95%CI = 1.355–6.646, P = 0.007). Furthermore, the rs10132552 CT genotype had a better response to treatment (OR = 0.261, 95%CI = 0.089–0.770, P = 0.015). Individuals carrying LINC-ROR rs2027701 with one or two variant alleles had significant associations with a reduced risk of neutropaenia (OR = 0.503, 95%CI = 0.303–0.835, P = 0.008). In conclusion, our results suggested that genetic polymorphisms of the lncRNA-p53 regulatory network could play a potential role in reducing treatment-related toxicities and improving outcomes for NPC patients.
- Published
- 2017
11. Long noncoding RNA expression signature to predict platinum-based chemotherapeutic sensitivity of ovarian cancer patients
- Author
-
Xi Li, Wei Zhang, Xiao-Ping Chen, Ying Zeng, Zhao-Qian Liu, Ying Wang, Rong Liu, Hong-Hao Zhou, and Cheng-Fang Zhou
- Subjects
0301 basic medicine ,Adult ,endocrine system diseases ,Science ,medicine.medical_treatment ,Antineoplastic Agents ,Platinum Compounds ,Biology ,Bioinformatics ,Article ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Cell Line, Tumor ,medicine ,Humans ,Aged ,Cisplatin ,Ovarian Neoplasms ,Chemotherapy ,Multidisciplinary ,Mesenchymal stem cell ,RNA ,Middle Aged ,medicine.disease ,Long non-coding RNA ,female genital diseases and pregnancy complications ,030104 developmental biology ,Cell culture ,030220 oncology & carcinogenesis ,Cancer research ,Medicine ,Female ,RNA, Long Noncoding ,Ovarian cancer ,medicine.drug - Abstract
Dysregulated long noncoding RNAs (lncRNAs) are potential markers of several tumor prognoses. This study aimed to develop a lncRNA expression signature that can predict chemotherapeutic sensitivity for patients with advanced stage and high-grade serous ovarian cancer (HGS-OvCa) treated with platinum-based chemotherapy. The lncRNA expression profiles of 258 HGS-OvCa patients from The Cancer Genome Atlas were analyzed. Results revealed that an eight-lncRNA signature was significantly associated with chemosensitivity in the multivariate logistic regression model, which can accurately predict the chemosensitivity of patients [Area under curve (AUC) = 0.83]. The association of a chemosensitivity predictor with molecular subtypes indicated the excellent prognosis performance of this marker in differentiated, mesenchymal, and immunoreactive subtypes (AUC > 0.8). The significant correlation between ZFAS1 expression and chemosensitivity was confirmed in 233 HGS-OvCa patients from the Gene Expression Omnibus datasets (GSE9891, GSE63885, and GSE51373). In vitro experiments demonstrated that the ZFAS1 expression was upregulated by cisplatin in A2008, HeyA8, and HeyC2 cell lines. This finding suggested that ZFAS1 may participate in platinum resistance. Therefore, the evaluation of the eight-lncRNA signature may be clinically implicated in the selection of platinum-resistant HGS-OvCa patients. The role of ZFAS1 in platinum resistance should be further investigated.
- Published
- 2017
12. Effect of carboxylesterase 1 S75N on clopidogrel therapy among acute coronary syndrome patients
- Author
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Min Liu, Bi-Lian Chen, Zhao-Qian Liu, Gan Zhou, Fei-Yan Xiao, Hong-Hao Zhou, Jian-Quan Luo, Shan Cao, and Wei Zhang
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Acute coronary syndrome ,Genotype ,Pharmacogenomic Variants ,Carboxylesterase 1 ,Science ,Comorbidity ,Pharmacology ,030226 pharmacology & pharmacy ,Gastroenterology ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,0302 clinical medicine ,Gene Frequency ,Polymorphism (computer science) ,Internal medicine ,medicine ,Humans ,Myocardial infarction ,cardiovascular diseases ,Acute Coronary Syndrome ,Allele frequency ,Alleles ,Aged ,Multidisciplinary ,Unstable angina ,business.industry ,Middle Aged ,medicine.disease ,Clopidogrel ,030104 developmental biology ,Treatment Outcome ,Amino Acid Substitution ,Purinergic P2Y Receptor Antagonists ,Medicine ,Female ,business ,Carboxylic Ester Hydrolases ,Platelet Aggregation Inhibitors ,medicine.drug - Abstract
Carboxylesterase 1 (CES1) hydrolyzes the prodrug clopidogrel to an inactive carboxylic acid metabolite. The effects of CES1 S75N (rs2307240,C>T) on clopidogrel response among 851 acute coronary syndrome patients who came from the north, central and south of China were studied. The occurrence ratios of each endpoint in the CC group were significantly higher than in the CT + TT group for cerebrovascular events (14% vs 4.8%, p CES1 S75N (rs2307240) and the outcome of clopidogrel therapy. Moreover, the frequency of the T allele of rs2307240 in acute coronary syndrome patients (MAF = 0.22) was more than four times higher than that in the general public (MAF = 0.05).
- Published
- 2016
13. Gene-gene and gene-environment interactions influence platinum-based chemotherapy response and toxicity in non-small cell lung cancer patients
- Author
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Zhao-Qian Liu, Hong-Hao Zhou, Jia-Jia Cui, Wei-Jing Gong, Tao Zhu, Ji-Ye Yin, and Lei-Yun Wang
- Subjects
0301 basic medicine ,Oncology ,Male ,medicine.medical_specialty ,Lung Neoplasms ,Abcg2 ,medicine.medical_treatment ,Science ,chemistry.chemical_element ,Single-nucleotide polymorphism ,Antineoplastic Agents ,Pharmacology ,Article ,03 medical and health sciences ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,Medicine ,Humans ,Lung cancer ,Gene ,Platinum ,Chemotherapy ,Multidisciplinary ,biology ,business.industry ,Reproducibility of Results ,Epistasis, Genetic ,Middle Aged ,medicine.disease ,ARHGAP26 ,030104 developmental biology ,chemistry ,Doxorubicin ,Toxicity ,biology.protein ,Female ,Gene-Environment Interaction ,business - Abstract
Platinum-based chemotherapy is a major therapeutic regimen of lung cancer. Various single nucleotide polymorphisms (SNPs) reported were associated with platinum-based chemotherapy response and drug toxicity. However, neither of the studies explored this association from SNP-SNP interaction perspective nor taking into effects of SNP-environment consideration simultaneously. We genotyped 504 polymorphisms and explore the association of gene-gene and gene-environment interactions with platinum-based chemotherapy response and toxicity in 490 NSCLC patients. 16 SNPs were found significantly associated with platinum-based chemotherapy, and they were picked out as study object in the validation cohort. We recruited 788 patients in the validation cohort. We found that HSPD1 rs17730989-SUMF1 rs2633851 interaction was associated with platinum-based chemotherapy-induced hematologic toxicity (adjusted OR = 0.233, P = 0.018). In addition, the combined effect of ABCG2 rs2231142-CES5A rs3859104 was significantly associated with overall toxicity (adjusted OR = 8.044, P = 4.350 × 10−5). Besides, the model of ARHGAP26 rs3776332-ERCC6 rs2228528-SLC2A1 rs4658-histology was associated with platinum-based chemotherapeutic response. Gene-gene and gene-environment interactions have been identified to contribute to chemotherapy sensitivity and toxicity. They can potentially predict drug response and toxicity of platinum-based chemotherapy in NSCLC patients.
- Published
- 2016
14. MiR-488 inhibits proliferation and cisplatin sensibility in non-small-cell lung cancer (NSCLC) cells by activating the eIF3a-mediated NER signaling pathway
- Author
-
Ji-Ye Yin, Wei Zhang, Zhao-Qian Liu, Yi-Xin Chen, Chao Fang, Hong-Hao Zhou, Na-Yiyuan Wu, Hsuan-Shun Huang, and Xiang-Ping Li
- Subjects
0301 basic medicine ,Lung Neoplasms ,DNA Repair ,Eukaryotic Initiation Factor-3 ,non-small cell lung cancer (NSCLC) ,Biology ,medicine.disease_cause ,Models, Biological ,Article ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,microRNA ,medicine ,Humans ,Neoplasm Invasiveness ,Author Correction ,Cell Proliferation ,Cisplatin ,A549 cell ,Multidisciplinary ,Base Sequence ,Cell growth ,medicine.disease ,Molecular biology ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Cell culture ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Carcinogenesis ,medicine.drug ,Nucleotide excision repair ,Signal Transduction - Abstract
Our previous studied indicated that eukaryotic translation initiation factor 3a (eIF3a) increases the sensitive of platinum-based chemotherapy in lung cancer. MiRNAs play an important role in lung carcinogenesis and drug response. In this study, we aimed to identify potential endogenous miRNAs that inhibit eIF3a expression and determine their influence of this inhibition on cisplatin resistance. Using bioinformatics analysis prediction and confirmation with dual-luciferase reporter assays, we found that miRNA-488 inhibited eIF3a expression by directly binding to the 3’UTR of eIF3a. In addition, the overexpression of miRNA-488 inhibited cell migration and invasion in A549 cells, and also inhibited cell proliferation, cell cycle progression by elevated P27 expression. Compared to the parental cell line, A549/cisplatin (DDP) resistant cells exhibited a higher level of miRNA-488. Moreover, we found that miRNA-488 was associated with cisplatin resistance in three NSCLC cells (A549, H1299 and SK-MES-1). The mechanism of miRNA-488 induced cisplatin resistance was that miRNA-488 activated nucleotide excision repair (NER) by increasing the expression of Replication Protein A (RPA) 14 and Xeroderma pigmentosum group C (XPC). In conclusion, our results demonstrated that miRNA-488 is a tumor suppressor miRNA that acts by targeting eIF3a. Moreover, miRNA-488 also participates in eIF3a mediated cisplatin resistance in NSCLC cells.
- Published
- 2016
15. SLCO1B1 Variants and Angiotensin Converting Enzyme Inhibitor (Enalapril) -Induced Cough: a Pharmacogenetic Study
- Author
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Zhao-Qian Liu, Gen-Fu Tang, Wei Zhang, Ning-Ling Sun, Lu-Yan Wang, Qing Li, Zhenmin Wang, Xiao-Ping Chen, Hong-Hao Zhou, Fa-Zhong He, Mou-Ze Liu, and Jian-Quan Luo
- Subjects
Male ,medicine.medical_specialty ,Gene Dosage ,Organic Anion Transporters ,Angiotensin-Converting Enzyme Inhibitors ,Pharmacology ,Essential hypertension ,Gastroenterology ,Polymorphism, Single Nucleotide ,Article ,Linkage Disequilibrium ,Enalapril ,Risk Factors ,Internal medicine ,Medicine ,Humans ,Genetic Predisposition to Disease ,Adverse effect ,Multidisciplinary ,biology ,business.industry ,Liver-Specific Organic Anion Transporter 1 ,Angiotensin-converting enzyme ,Middle Aged ,medicine.disease ,Cough ,Haplotypes ,Enalapril Maleate ,Pharmacogenetics ,Relative risk ,biology.protein ,Female ,business ,SLCO1B1 ,medicine.drug - Abstract
Clinical observations suggest that incidence of cough in Chinese taking angiotensin converting enzyme inhibitors is much higher than other racial groups. Cough is the most common adverse reaction of enalapril. We investigate whether SLCO1B1 genetic polymorphisms, previously reported to be important determinants of inter-individual variability in enalapril pharmacokinetics, are associated with the enalapril-induced cough. A cohort of 450 patients with essential hypertension taking 10 mg enalapril maleate were genotyped for the functional SLCO1B1 variants, 388A > G (Asn130Asp, rs2306283) and 521T > C (Val174Ala, rs4149056). The primary endpoint was cough, which was recorded when participants were bothered by cough and respiratory symptoms during enalapril treatment without an identifiable cause. SLCO1B1 521C allele conferred a 2-fold relative risk of enalapril-induced cough (95% confidence interval [CI] = 1.34–3.04, P = 6.2 × 10−4) and haplotype analysis suggested the relative risk of cough was 6.94-fold (95% CI = 1.30–37.07, P = 0.020) in SLCO1B1*15/*15 carriers. Furthermore, there was strong evidence for a gene-dose effect (percent with cough in those with 0, 1, or 2 copy of the 521C allele: 28.2%, 42.5% and 71.4%, trend P = 6.6 × 10−4). Our study highlights, for the first time, SLCO1B1 variants are strongly associated with an increased risk of enalapril-induced cough. The findings will be useful to provide pharmacogenetic markers for enalapril treatment.
- Published
- 2015
- Full Text
- View/download PDF
16. Genome-scale long noncoding RNA expression pattern in squamous cell lung cancer
- Author
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Xiang-Ping Li, Yi Zheng, Yi-Lan Fu, Zhao-Qian Liu, Hui Zhou, Ying Wang, Juan Chen, Lin Xiao, Chen-Yue Qian, Rong-Rong Liu, Xiao-Jing Xu, Zi-Yu Chen, Cheng-Cheng Ye, Hui-Juan He, Ji-Ye Yin, Wei Zhang, Jing-jing Wang, Yu Zhang, Xiang Chen, Hong-Hao Zhou, and Jia-Jia Cui
- Subjects
Adult ,Male ,Lung Neoplasms ,Microarray ,Biology ,Real-Time Polymerase Chain Reaction ,Article ,medicine ,Humans ,Gene Regulatory Networks ,RNA, Messenger ,Lung cancer ,Lung ,Aged ,Oligonucleotide Array Sequence Analysis ,Regulation of gene expression ,Multidisciplinary ,Genome, Human ,RNA ,Middle Aged ,Cell cycle ,medicine.disease ,Molecular biology ,Long non-coding RNA ,Gene Expression Regulation, Neoplastic ,Real-time polymerase chain reaction ,Case-Control Studies ,Carcinoma, Squamous Cell ,Female ,RNA, Long Noncoding ,Human genome - Abstract
In this study, we aimed to explore the long noncoding RNA expression pattern in squamous cell lung cancer (SQCC) on a genome-wide scale. Total RNAs were extracted from 16 lung SQCC patients’ normal and matched lung cancer tissues by Trizol reagent. The expression level of genome-wide scale lncRNA and mRNA was determined by microarray. qRT-PCR was used to validate the lncRNA expression level in 47 patients. Data analyses were performed using R and Bioconductor. A total of 2,748 up and 852 down regulated probes were identified to be significantly and differentially expressed in tumor tissues. The annotation result of their co-expressed mRNAs showed that the most significantly related category of GO analysis was development and differentiation, while the most significantly related pathway was cell cycle. Subgroup analysis identified that 46 and 18 probes were specifically differentially expressed in smoking and moderately differentiated tumors, respectively. Our study indicated that clusters of lncRNAs were significantly and differentially expressed in SQCC compared with normal tissues in the same subject. They may exert a significant role in lung cancer development and could be potential targets for future treatment of SQCC.
- Published
- 2015
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