Pharmacogenomics & Personalized Medicine最新文献

{"title":"LncRNA FOXD2-AS1 Increased Proliferation and Invasion of Lung Adenocarcinoma via Cell-Cycle Regulation.","authors":"Yuan Yuan,&nbsp;Peng Yu,&nbsp;Huihua Shen,&nbsp;Guozhu Xing,&nbsp;Wu Li","doi":"10.2147/PGPM.S396866","DOIUrl":"https://doi.org/10.2147/PGPM.S396866","url":null,"abstract":"<p><strong>Background: </strong>Long non-coding RNA FOXD2 antisense RNA 1 (FOXD2-AS1) has been reported in many malignancies. However, the molecular mechanism of many actions is not clarified. This study was conducted to investigate the function of FOXD2-AS1 in lung adenocarcinoma and its molecular mechanism.</p><p><strong>Methods: </strong>Bioinformatics and in vitro analysis including RT-qPCR, CFU, CCK8, Transwell, Cell Apoptosis and Cell Cycle Assay were used for the analysis of gene expression and related effects.</p><p><strong>Results: </strong>It revealed increased expression of lncRNA FOXD2-AS1 in lung adenocarcinoma cell lines (A549 cells), and abundant expression of lncRNA FOXD2-AS1 was also observed in the acquired lung adenocarcinoma tissues. In vitro results showed that knockdown of lncRNA FOXD2-AS1 in A549 cells weakened cell proliferation, invasion and increased apoptosis. At the same time, we found that reducing the expression of lncRNA FOXD2-AS1 caused cell cycle arrest in the G1/S phase. Differential gene analysis of lung adenocarcinoma and adjacent normal tissues showed that the cell cycle and its related process regulation were significantly enriched. Gene Set Enrichment Analysis (GSEA) analysis showed that miR-206, miR-143, lL6-JAK-STAT3 signalling pathway, STAT3, E2F targets, EZH2, P53 signalling pathway and E2F3 targets interacting with lncRNA FOXD2-AS1 were also enriched.</p><p><strong>Conclusion: </strong>This study demonstrates the role and mechanism of the lncRNA FOXD2-AS1 in lung adenocarcinoma and provides a better understanding for the treatment of lung adenocarcinoma, which indicates that interfering with lncRNA FOXD2-AS1 expression may be a novel strategy.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"99-109"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1c/22/pgpm-16-99.PMC9904230.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10687614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: A Novel Homozygous Mutation of Cyclin O Gene Mutation in Primary Ciliary Dyskinesia with Short Stature.","authors":"Dai Gong,&nbsp;Qiong Tang,&nbsp;Li-Juan Yan,&nbsp;Xiao-Min Ye,&nbsp;Yi-Can Yang,&nbsp;Li Zou,&nbsp;Qing Ji,&nbsp;Xiang-Lan Wen","doi":"10.2147/PGPM.S406445","DOIUrl":"https://doi.org/10.2147/PGPM.S406445","url":null,"abstract":"<p><strong>Background: </strong>Primary ciliary dyskinesia (PCD) is a group of autosomal recessive genetic diseases caused by abnormal ciliary ultrastructure and/or function, resulting in reduced ciliary clearance function or other dysfunctions. PCD is one of the causes of recurrent respiratory tract infections in children. At present, there is no gold standard for diagnosis. In patients clinically suspected with PCD, a variety of examination methods are available to assist in diagnosis, such as high-speed video microscopic imaging to analyze ciliary movement patterns, transmission electron microscopy to observe ciliary ultrastructure, genetic testing, and detection of nitric oxide content in nasal expiratory air.</p><p><strong>Case description: </strong>We present a case summary of the clinical data and treatment process of a child with PCD and short stature induced by Novel exon 1 of CCNO mutation (NM-021147.5) at c.323del, and the proband father and mother were heterozygous mutators, who was diagnosed and treated in the Pediatric Healthcare Department of our hospital. We treated the child with recombinant human growth hormone to increase the height, and the patient was also advised to improve nutrition, prevent and control infections, and encouraged sputum expectoration. We also recommended regular follow-up visits to the outpatient department, and to seek other symptomatic and supportive treatments as necessary.</p><p><strong>Conclusion: </strong>The height and nutritional status of the child improved after treatment. We also reviewed relevant literature to help clinicians improve their understanding of this disease.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"443-448"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8b/6c/pgpm-16-443.PMC10200132.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9515724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Giant Multilocular-Cystic Metaplastic Thymoma: A Case Report.","authors":"Lihua Han,&nbsp;Bo Gao,&nbsp;En-Hua Wang,&nbsp;Liang Wang","doi":"10.2147/PGPM.S413757","DOIUrl":"https://doi.org/10.2147/PGPM.S413757","url":null,"abstract":"<p><p>The metaplastic thymoma with giant multilocular-cyst formation had not been documented. The metaplastic thymoma is an extremely rare primary thymic epithelial tumor with an indolent clinical course. It is characterized by a histologic biphasic appearance, which is consisted of solid epithelial areas and spindle cells as the background. This specific pattern can be easily mistaken as the type A thymoma or the type A components of type AB thymoma. When cystic change occurs in metaplastic thymoma, it will bring more challenges for both imaging and pathological diagnosis. Herein, we reported an extremely rare case of a 14.9-cm giant tumor located in the anterior mediastinum of an elderly female. The tumor is consisted of both multilocular cysts and solid components, with the largest cyst measuring 6 cm in diameter. The multilocular cyst contained hemorrhage, calcification, and cholesterol crystal cracks without cell lining. In the solid area, the epithelial cell nests were surrounded by spindle cells with scattered lymphocytes. With immunostains, neither type of cells was CD20 positive. The epithelial cells were positive for CK and P63, while the spindle cells expressed vimentin and EMA. Fluorescence in situ hybridization analysis revealed that the tumor harbored <i>YAP1-MAML2</i> gene fusions. Accordingly, although the multilocular cystic pattern set a diagnostic challenge, the diagnosis of metaplastic thymoma was rendered due to the immunohistochemistry staining and <i>YAP1-MAML2</i> gene rearrangement detection.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"463-466"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c4/1f/pgpm-16-463.PMC10204752.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9527047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One Rare Warfarin Resistance Case and Possible Mechanism Exploration.","authors":"Li Zhao,&nbsp;Zhenguo Zhai,&nbsp;Pengmei Li","doi":"10.2147/PGPM.S404474","DOIUrl":"https://doi.org/10.2147/PGPM.S404474","url":null,"abstract":"<p><p>One 59-year-old female patient with deep venous thrombosis (DVT) and pulmonary embolism (PE) was treated with 6 mg warfarin once daily as an anticoagulant. Before taking warfarin, her international normalized ratio (INR) was 0.98. Two days after warfarin treatment, her INR did not change from baseline. Due to the high severity of the PE, the patient needed to reach her target range (INR goal = 2.5, range = 2~3) rapidly, so the dose of warfarin was increased from 6 mg daily to 27 mg daily. However, the patient's INR did not improve with the dose escalation, still maintaining an INR of 0.97-0.98. We drew a blood sample half an hour before administering 27 mg warfarin and detected single nucleotide polymorphism for the following genes, which were identified to be relevant with warfarin resistance: CYP2C9 rs1799853, rs1057910, VKORC1 rs9923231, rs61742245, rs7200749, rs55894764, CYP4F2 rs2108622, and GGCX rs2592551. The trough plasma concentration of warfarin was 196.2 ng/mL after 2 days of warfarin administration with 27 mg QD, which was much lower than the therapeutic drug concentration ranges of warfarin (500-3,000 ng/mL). The genotype results demonstrate that the CYP4F2gene has rs2108622 mutation which can explain some aspect of warfarin resistance. Further investigations are necessary to fully characterize other pharmacogenomics or pharmacodynamics determinants of warfarin dose-response in Chinese.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"609-615"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/02/08/pgpm-16-609.PMC10290475.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9714671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Relationship Between <i>MMP17</i> Variants and Ischemic Stroke Risk in the Population from Shaanxi Province in China.","authors":"Weiping Li,&nbsp;Yanqing Liu,&nbsp;Xiaoling Xu,&nbsp;Qi Zhang,&nbsp;Xiao Zhang,&nbsp;Jie Zhang,&nbsp;Xiaochen Niu,&nbsp;Shiyao Yang,&nbsp;Xiaobo Zhang,&nbsp;Wenzhen Shi,&nbsp;Gejuan Zhang,&nbsp;Mingze Chang,&nbsp;Ye Tian","doi":"10.2147/PGPM.S396076","DOIUrl":"https://doi.org/10.2147/PGPM.S396076","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke (IS) was a multifactorial disease, which was the main cause of death and adult disability. Genetic factors cannot be ignored.</p><p><strong>Objective: </strong>The present study discussed the relationship between <i>MMP17</i> variants and the susceptibility of IS.</p><p><strong>Methods: </strong>Based on the Agena MassARRAY platform, we genotyped single nucleotide polymorphisms (SNPs) on the <i>MMP17</i> gene in 1345 participants (670 controls and 675 cases). We used logistic regression analysis to analyze the association of <i>MMP17</i> SNPs with the risk of IS in the Chinese population, with odds ratio (OR) and 95% confidence intervals (CIs). False-positive report probability (FPRP) detected false positives on the significant results. Besides, we detected the SNP-SNP interaction to predict IS risk by multi-factor dimensionality reduction (MDR) analysis.</p><p><strong>Results: </strong>In the total analysis, <i>MMP17</i> rs7975920 conferred an increased susceptibility to IS. After a stratified analysis by age and gender, the significant association between rs7975920 and IS risk was displayed in the subjects aged >55 years old and females. After stratified analysis by smoking and drinking, <i>MMP17</i> rs6598163 was related to the risk of IS in smokers and rs7975920 was associated with the risk of IS in smokers and was in correlation with IS risk in drinkers.</p><p><strong>Conclusion: </strong>In short, we first observed that <i>MMP17</i> rs7975920 and rs6598163 were related to the risk of IS. The above results provided a theoretical basis for the elaboration of the role of MMP17 in IS in the Chinese population.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"59-66"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2d/2d/pgpm-16-59.PMC9889100.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9198030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Preliminary Study on the Correlation Between Age and Endometrial Receptivity.","authors":"Song Guo,&nbsp;Di Zhang,&nbsp;Shan Zhao,&nbsp;Huan Zhang,&nbsp;Yijuan Sun,&nbsp;Li Yan","doi":"10.2147/PGPM.S406257","DOIUrl":"https://doi.org/10.2147/PGPM.S406257","url":null,"abstract":"<p><strong>Background: </strong>It is well established that female fertility declines with age, primarily because of loss of ovarian function. However, few studies have clarified the relationship between increasing age and endometrial receptivity. Here, we aimed to study the impact of age on endometrial receptivity, meanwhile, we examined the expression of endometrial mesenchymal stem cell (eMSC) surface markers (CD146 and PDGF-Rβ), essential for endometrial development and re-growth, in different age groups.</p><p><strong>Methods: </strong>Participants were enrolled in this study between October 2020 and July 2021. All 31 patients were divided into three age groups; early (30-39 years old, n=10), intermediate (40-49 years old, n=12) and advanced (≥50 years old, n=9). We assessed localization and expression of CD146 and PDGF-Rβ by immunofluorescence and further analyzed selected endometrial receptivity markers (Homeobox A10 HOXA10, leukemia inhibitory factor LIF and osteopontin) and steroid hormone receptors by immunohistochemistry.</p><p><strong>Results: </strong>There were no significant differences in expression of HOXA10 and OPN (p>0.05) among the three groups. However, we found a significant difference in LIF expression between the early and advanced age groups, with higher expression noted in the latter group (p=0.02). Similarly, estrogen receptor (ER) and progesterone receptor (PR) expression were significantly increased (p=0.01 and p=0.01, respectively) in the advanced age group compared with the early age group. There were no significant difference in CD146 and PDGF-Rβ expression among the three groups (p>0.05).</p><p><strong>Conclusion: </strong>These results suggest that the age of the patient does not influence their endometrial receptivity. So, this study serves to increase our understanding of the impact of age and eMSCs on endometrial receptivity and expands the etiology of age-related infertility.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"425-432"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/28/40/pgpm-16-425.PMC10171358.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9468587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of Drug-Responsive Phenomic Alteration-Related Driver Genes in the Treatment of Coronary Heart Disease.","authors":"Shuang Guan,&nbsp;Ya-Nan Yu,&nbsp;Bing Li,&nbsp;Hao Gu,&nbsp;Lin Chen,&nbsp;Nian Wang,&nbsp;Bo Wang,&nbsp;Xi Liu,&nbsp;Jun Liu,&nbsp;Zhong Wang","doi":"10.2147/PGPM.S398522","DOIUrl":"https://doi.org/10.2147/PGPM.S398522","url":null,"abstract":"Background The Xueyu Zheng (XYZ) phenome is central to coronary heart disease (CHD), but efforts to detect genetic associations in the XYZ phenome have been disappointing. Methods The phenomic alteration-related genes (PARGs) for the XYZ phenome were screened using |ρ| > 0.4 and p < 0.05 after treatment with Danhong injection at day 14 and day 30. Then, the driver genes for the Protein-Protein Interaction (PPI) networks of the PARGs established using STRING 11.0 were detected using a personalized network control algorithm (PNC). Finally, the molecular correlations of the driver genes with the XYZ phenome were analyzed with the Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways from a holistic viewpoint. Results A total of 525 and 309 PARGs in the XYZ phenome at day 14 and day 30 were identified. These genes were separately enriched in 48 and 35 pathways. Furthermore, five driver genes were detected. These genes were mainly correlated with endoplasmic reticulum stress-mediated apoptosis and autophagy regulation, which could suppress atherosclerosis progression. Conclusion Our study detected the drug-responsive PARGs of the XYZ phenome in CHD and provides an exemplary strategy to investigate the genetic associations among this common phenome and its component symptoms in patients with CHD. Trial Registration ClinicalTrials.gov, NCT01681316; registered on September 7, 2012.","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"201-217"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/98/18/pgpm-16-201.PMC10024908.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9513447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Influence of Cytochrome P450 Polymorphisms on Pharmacokinetic Profiles and Treatment Outcomes Among Malaria Patients in Sub-Saharan Africa: A Systematic Review.","authors":"Karol J Marwa,&nbsp;Anthony Kapesa,&nbsp;Erasmus Kamugisha,&nbsp;Göte Swedberg","doi":"10.2147/PGPM.S379945","DOIUrl":"https://doi.org/10.2147/PGPM.S379945","url":null,"abstract":"<p><strong>Background: </strong>Sub-Saharan Africa (SSA) population is genetically diverse and heterogenous thus variability in drug response among individuals is predicted to be high. Cytochrome P450 (CYP450) polymorphisms is a major source of variability in drug response. This systematic review presents the influence of CYP450 single nucleotide polymorphisms (SNPs), particularly CYP3A4*1B, CYP2B6*6 and CYP3A5*3 on antimalarial drug plasma concentrations, efficacy and safety in SSA populations.</p><p><strong>Methods: </strong>Searching for relevant studies was done through Google Scholar, Cochrane Central Register of controlled trials (CENTRAL), PubMed, Medline, LILACS, and EMBASE online data bases. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used. Two independent reviewers extracted data from the studies.</p><p><strong>Results: </strong>Thirteen studies reporting the influence of CYP450 SNPs on plasma concentrations, efficacy and safety were included in the final data synthesis. CYP3A4*1B, CYP3A5*5, CYP2B6*6 and CYP2C8*2 did not affect antimalarial drug plasma concentration significantly. There was no difference in treatment outcomes between malaria patients with variant alleles and those with wild type alleles.</p><p><strong>Conclusion: </strong>This review reports lack of influence of CYP3A4*1B, CYP3A5*3, CYP2C8*3 and CYP2B6*6 SNPs on PK profiles, efficacy and safety in SSA among <i>P. falciparum</i> malaria patients.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"449-461"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fd/bc/pgpm-16-449.PMC10202199.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9518986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mental Health Prescribers' Perceptions on the Use of Pharmacogenetic Testing in the Management of Depression in the Middle East and North Africa Region.","authors":"Shimaa Aboelbaha,&nbsp;Monica Zolezzi,&nbsp;Oraib Abdallah,&nbsp;Yassin Eltorki","doi":"10.2147/PGPM.S410240","DOIUrl":"https://doi.org/10.2147/PGPM.S410240","url":null,"abstract":"<p><strong>Objective: </strong>A wide variety of commercial pharmacogenetic (PGx) tools are available worldwide to guide treatment selection for depression based on individuals' genetic profiles. However, the use of genetic testing to inform psychiatric care has faced challenges due to the limited training and education for mental health clinicians. The aim of this study was to explore the knowledge, level of engagement, and perspectives on the use of PGx testing when making depression management decisions among practicing psychiatrists within the Middle East and North Africa (MENA) region.</p><p><strong>Methods: </strong>This is a qualitative study using semi-structured interviews. Consenting psychiatrists were interviewed through an online platform (Skype^TM or Microsoft Teams^TM). Interviews were audio recorded, transcribed, and thematically analyzed with the assistance of NVivo^® software.</p><p><strong>Results: </strong>Eighteen interviews from 12 countries have been conducted. Analysis of the current interviews produced five major themes including: (1) Overall perceptions and attitudes; (2) Knowledge and awareness; (3) Education, training, and professional experience; (4) Facilitators and barriers; and (5) Ethical dilemmas. These themes support the notion that there is limited, mostly basic, education, knowledge, and training regarding genetic testing in the management of depression, although there is significant interest and willingness in the part of prescribers to adopt this strategy in their practice.</p><p><strong>Conclusion: </strong>The findings of the study suggest that psychiatrists practicing in the MENA region appear to be interested in implementing PGx testing when managing people with depression. However, it is also important to recognize that this cannot be achieved unless more supporting strategies are implemented within their current health system environment.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"503-518"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10239256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9934982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Allelic Expression of RNA Editing Gene <i>ADARB1</i> in Hepatocellular Carcinoma Treated with Transarterial Chemoembolization.","authors":"Jiajia Zeng,&nbsp;Linyu Han,&nbsp;Teng Wang,&nbsp;Linying Huang,&nbsp;Yanxiu Zheng,&nbsp;Nasha Zhang,&nbsp;Ziqiang Li,&nbsp;Ming Yang","doi":"10.2147/PGPM.S402115","DOIUrl":"https://doi.org/10.2147/PGPM.S402115","url":null,"abstract":"<p><strong>Introduction: </strong>Transarterial chemoembolization (TACE) is the commonly used therapy of unresectable hepatocellular carcinoma (HCC), though the prognosis of different TACE-treated HCC patients varies, which may be due to the heterogeneity of HCC tumors caused by genetic variants and epigenetic changes such as RNA editing. There is dysregulated RNA adenosine-to-inosine (A-to-I) editing in HCC and RNA-edited genes are involved in the epigenetic process. It remains unclear how genetic variants of RNA editing genes affect the prognosis of HCC cases treated by TACE.</p><p><strong>Methods: </strong>In this study, we examined 28 potentially functional single-nucleotide polymorphisms (SNPs) of four RNA editing genes (<i>ADARB1, ADAR, ADARB2</i> and <i>AIMP2</i>) in two independent TACE patient cohorts.</p><p><strong>Results: </strong>We found that <i>ADARB1</i> rs1051367 and rs2253763 polymorphisms were markedly associated with the prognosis of HCC cases who received TACE in both cohorts. In HCC cells, the rs2253763 C-to-T change in <i>ADARB1</i> 3'-untranslated region attenuated its binding with miR-542-3p and allele-specifically elevated <i>ADARB1</i> levels. Consistent with this, patients carrying the rs2253763 C allele showed reduced <i>ADARB1</i> expression in cancer tissues and notably shorter survival after TACE therapy in comparison with individuals with the T allele. Ectopic <i>ADARB1</i> profoundly enhanced the efficacy of oxaliplatin, one of the common TACE chemotherapeutic drugs.</p><p><strong>Discussion: </strong>Our findings highlighted the value of <i>ADARB1</i> polymorphisms as prognostic markers in TACE therapy for HCC patients. Notably, our findings revealed that targeting the ADARB1 enzyme may be a promising therapeutic strategy in combination with TACE for HCC cases.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"229-238"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c4/e7/pgpm-16-229.PMC10032144.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9194066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}