Pub Date : 2025-01-03DOI: 10.1007/s10528-024-11001-2
Bingqiang Zhang, Xiaoyan Ma, Yang Zhou, Boyang Zhu, Junmei Yu, He Liu, Yongchao Ma, Yansong Luan, Mengmeng Chen
Mounting evidence suggests that circulating microRNAs (miRNAs) hold diagnostic value in various malignancies. To identify circulating miRNAs for the early diagnosis of hepatocellular carcinoma (HCC), we conducted a meta-analysis to evaluate the diagnostic utility of miRNAs in HCC and further validated the results of the meta-analysis. English articles published prior to December 2023 were retrieved from databases including PubMed, Embase, and Web of Science. A random-effects or fixed-effects model was applied depending on the heterogeneity among studies. The pooled sensitivity, specificity, and the area under the summary receiver operating characteristic curve (AUC) were calculated to assess diagnostic accuracy. Additionally, RT-qPCR and receiver operating characteristic (ROC) analyses were employed to further validate the findings. A total of 36 studies were included, involving 3362 patients with HCC and 2150 patients with chronic hepatitis. The pooled sensitivity, specificity, and diagnostic odds ratio were 0.79 (95% CI 0.75-0.82), 0.79 (95% CI 0.73-0.84), and 14 (95% CI 9-22), respectively; the positive and negative likelihood ratios were 4.0 and 0.27, respectively; the area under the curve (AUC) in the summary receiver operating characteristic (ROC) was 0.85 (95% CI 0.82-0.88). Validation indicated a significant upregulation of miR-1246, miR-21, and miR-221 in HCC patients compared to those with chronic hepatitis (P < 0.01), while miR-122 and miR-26a were significantly downregulated (P < 0.01). Moreover, the validation results also demonstrated that serum levels of miR-21, miR-26a, miR-122, miR-221, and miR-1246 exhibit high sensitivity and specificity in the diagnosis of HCC. Circulating miRNAs may be promising biomarkers for HCC diagnosis.
越来越多的证据表明,循环microRNAs (miRNAs)在各种恶性肿瘤中具有诊断价值。为了确定用于肝细胞癌(HCC)早期诊断的循环mirna,我们进行了一项荟萃分析,以评估mirna在HCC中的诊断效用,并进一步验证了荟萃分析的结果。从PubMed、Embase和Web of Science等数据库检索2023年12月之前发表的英文文章。根据研究间的异质性,采用随机效应或固定效应模型。计算合并敏感性、特异性和总受者工作特征曲线下面积(AUC)来评估诊断准确性。此外,采用RT-qPCR和受试者工作特征(ROC)分析进一步验证研究结果。共纳入36项研究,涉及3362例HCC患者和2150例慢性肝炎患者。合并敏感性、特异性和诊断优势比分别为0.79 (95% CI 0.75-0.82)、0.79 (95% CI 0.73-0.84)和14 (95% CI 9-22);正似然比为4.0,负似然比为0.27;总体受试者工作特征(ROC)曲线下面积(AUC)为0.85 (95% CI 0.82 ~ 0.88)。验证表明,与慢性肝炎患者相比,HCC患者中miR-1246、miR-21和miR-221显著上调(P
{"title":"Diagnostic Value of Circulating microRNAs for Hepatocellular Carcinoma: Results of a Meta-analysis and Validation.","authors":"Bingqiang Zhang, Xiaoyan Ma, Yang Zhou, Boyang Zhu, Junmei Yu, He Liu, Yongchao Ma, Yansong Luan, Mengmeng Chen","doi":"10.1007/s10528-024-11001-2","DOIUrl":"https://doi.org/10.1007/s10528-024-11001-2","url":null,"abstract":"<p><p>Mounting evidence suggests that circulating microRNAs (miRNAs) hold diagnostic value in various malignancies. To identify circulating miRNAs for the early diagnosis of hepatocellular carcinoma (HCC), we conducted a meta-analysis to evaluate the diagnostic utility of miRNAs in HCC and further validated the results of the meta-analysis. English articles published prior to December 2023 were retrieved from databases including PubMed, Embase, and Web of Science. A random-effects or fixed-effects model was applied depending on the heterogeneity among studies. The pooled sensitivity, specificity, and the area under the summary receiver operating characteristic curve (AUC) were calculated to assess diagnostic accuracy. Additionally, RT-qPCR and receiver operating characteristic (ROC) analyses were employed to further validate the findings. A total of 36 studies were included, involving 3362 patients with HCC and 2150 patients with chronic hepatitis. The pooled sensitivity, specificity, and diagnostic odds ratio were 0.79 (95% CI 0.75-0.82), 0.79 (95% CI 0.73-0.84), and 14 (95% CI 9-22), respectively; the positive and negative likelihood ratios were 4.0 and 0.27, respectively; the area under the curve (AUC) in the summary receiver operating characteristic (ROC) was 0.85 (95% CI 0.82-0.88). Validation indicated a significant upregulation of miR-1246, miR-21, and miR-221 in HCC patients compared to those with chronic hepatitis (P < 0.01), while miR-122 and miR-26a were significantly downregulated (P < 0.01). Moreover, the validation results also demonstrated that serum levels of miR-21, miR-26a, miR-122, miR-221, and miR-1246 exhibit high sensitivity and specificity in the diagnosis of HCC. Circulating miRNAs may be promising biomarkers for HCC diagnosis.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142919002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-29DOI: 10.1007/s10528-024-11003-0
Xia Qi, Anwar Ullah, Weijian Yu, Xiaojun Jin, Hui Liu
This study aims to establish a genetic risk assessment model based on a score of short tandem repeats (STRs) of polygenic inheritance. A total of 396 children and their biological parents were collected for STR genotyping. The numbers of tandem repeats of two alleles in one STR locus were assumed to be a quantitative genetic strength for disease incidence. The sums of 19 STR loci were considered a quantitative genetic strength per individual. Various thresholds of the STRs between paternal, maternal, and childhood data were recorded. As an exemplar, for thresholds of 25%, the first quarter = 1. All other samples = 0. The consistency rate for heredity (CH) was calculated from the difference in the morbidity of children between parents with and without disease groups. The ratio of observed CH to expected CH was defined as the heredity index (HI). Actual Pedigree data (finger-crossing test) confirmed the accuracy of the STR score. The genetic risk of first-degree relatives could be estimated using easily acquired data (incidence in an unrelated population). Our findings can provide a polygenic genetic model for estimating the incidence and genetic risk of chronic disease in first-degree relatives.
{"title":"Estimating the Genetic Risk of First-Degree Relatives for Chronic Diseases Using the Short Tandem Repeat Score as Model of Polygenic Inheritance.","authors":"Xia Qi, Anwar Ullah, Weijian Yu, Xiaojun Jin, Hui Liu","doi":"10.1007/s10528-024-11003-0","DOIUrl":"https://doi.org/10.1007/s10528-024-11003-0","url":null,"abstract":"<p><p>This study aims to establish a genetic risk assessment model based on a score of short tandem repeats (STRs) of polygenic inheritance. A total of 396 children and their biological parents were collected for STR genotyping. The numbers of tandem repeats of two alleles in one STR locus were assumed to be a quantitative genetic strength for disease incidence. The sums of 19 STR loci were considered a quantitative genetic strength per individual. Various thresholds of the STRs between paternal, maternal, and childhood data were recorded. As an exemplar, for thresholds of 25%, the first quarter = 1. All other samples = 0. The consistency rate for heredity (CH) was calculated from the difference in the morbidity of children between parents with and without disease groups. The ratio of observed CH to expected CH was defined as the heredity index (HI). Actual Pedigree data (finger-crossing test) confirmed the accuracy of the STR score. The genetic risk of first-degree relatives could be estimated using easily acquired data (incidence in an unrelated population). Our findings can provide a polygenic genetic model for estimating the incidence and genetic risk of chronic disease in first-degree relatives.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-28DOI: 10.1007/s10528-024-10998-w
Jinhe Chen, Fan Liu, Xianwei Meng
Recent studies highlight the crucial role of microRNAs (miRNAs) in coronary artery disease (CAD). This retrospective study investigated the abundance of miR-432-5p in the serum of CAD patients and explored its role. 252 volunteers were included. The levels of miR-432-5p and Sortilin 1 (SORT1) in the serum of CAD patients and oxidized low-density lipoprotein (ox-LDL)-treated human arterial smooth muscle cells (HASMCs) were quantified via qRT-PCR. The correlation coefficient, clinical diagnostic performance, and risk factors were analyzed with Pearson correlation, receiver operating characteristic (ROC) curve, and binomial logistic regression, respectively. HASMC proliferation, migration, and apoptosis were evaluated using Cell Counting Kit-8 (CCK-8), transwell, and flow cytometry assay, respectively. Potential binding sites between miR-432-5p and SORT1 were predicted with TargetScan and validated through dual-luciferase reporter assay and co-transfection experiments. Serum miR-432-5p was decreased, while SORT1 was elevated in CAD patients and ox-LDL-induced HASMCs. miR-432-5p showed a negative correlation with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), and Gensini score. miR-432-5p and SORT1 effectively distinguished CAD patients from controls based on ROC analysis. miR-432-5p and SORT1 serve as independent risk predictors. Restoration of miR-432-5p reversed ox-LDL-induced increases in HASMC proliferation and migration and restored apoptosis levels. SORT1 was confirmed as a direct target of miR-432-5p, and its upregulation counteracted the protective effects of miR-432-5p on HASMC under ox-LDL exposure. This study suggests that miR-432-5p protects HASMCs and inhibits coronary artery disease progression by targeting SORT1, positioning both miR-432-5p and SORT1 as potential biomarkers for CAD.
{"title":"miR-432-5p Targeting SORT1 to Protect Artery Smooth Muscle Cells and Inhibit Coronary Artery Disease.","authors":"Jinhe Chen, Fan Liu, Xianwei Meng","doi":"10.1007/s10528-024-10998-w","DOIUrl":"https://doi.org/10.1007/s10528-024-10998-w","url":null,"abstract":"<p><p>Recent studies highlight the crucial role of microRNAs (miRNAs) in coronary artery disease (CAD). This retrospective study investigated the abundance of miR-432-5p in the serum of CAD patients and explored its role. 252 volunteers were included. The levels of miR-432-5p and Sortilin 1 (SORT1) in the serum of CAD patients and oxidized low-density lipoprotein (ox-LDL)-treated human arterial smooth muscle cells (HASMCs) were quantified via qRT-PCR. The correlation coefficient, clinical diagnostic performance, and risk factors were analyzed with Pearson correlation, receiver operating characteristic (ROC) curve, and binomial logistic regression, respectively. HASMC proliferation, migration, and apoptosis were evaluated using Cell Counting Kit-8 (CCK-8), transwell, and flow cytometry assay, respectively. Potential binding sites between miR-432-5p and SORT1 were predicted with TargetScan and validated through dual-luciferase reporter assay and co-transfection experiments. Serum miR-432-5p was decreased, while SORT1 was elevated in CAD patients and ox-LDL-induced HASMCs. miR-432-5p showed a negative correlation with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), and Gensini score. miR-432-5p and SORT1 effectively distinguished CAD patients from controls based on ROC analysis. miR-432-5p and SORT1 serve as independent risk predictors. Restoration of miR-432-5p reversed ox-LDL-induced increases in HASMC proliferation and migration and restored apoptosis levels. SORT1 was confirmed as a direct target of miR-432-5p, and its upregulation counteracted the protective effects of miR-432-5p on HASMC under ox-LDL exposure. This study suggests that miR-432-5p protects HASMCs and inhibits coronary artery disease progression by targeting SORT1, positioning both miR-432-5p and SORT1 as potential biomarkers for CAD.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-28DOI: 10.1007/s10528-024-11011-0
Huimin Wang, Yi Yang, Enjing Zhang, Dan Wang, Weiqiong Cai, Chun Li, Qiong Wei
Cisplatin, a platinum-based chemotherapeutic agent, can be used to treat cervical cancer (CC), but cisplatin resistance is increased during the cisplatin treatment. Long non-coding RNA PGM5-AS1 reportedly participates in CC tumorigenesis; however, its role in CC patients with cisplatin resistance has not been revealed. The present aimed to examine the role of PGM5-AS1 in modulating cisplatin resistance in CC. The PGM5-AS1 expression in CC tissues from 29 patients was quantified using quantitative reverse transcription-polymerase chain reaction. The cisplatin-resistant CC cells were constructed by using increasing cisplatin concentrations. The effects of cisplatin resistance interacting with PGM5-AS1 on CC cell malignancy were confirmed by performing Cell Counting Kit 8, colony formation, wound healing, and transwell assays. The key proteins of the Hippo and PI3K-AKT signaling pathways were evaluated by Western blotting. PGM5-AS1 with low expression in CC tissues was correlated to higher International Federation of Gynecology and Obstetrics stage, poor differentiation, lymph node metastasis, and cisplatin resistance. PGM5-AS1 overexpression suppressed the proliferation, migration, and invasion abilities of cisplatin-resistant CC cells. Additionally, PGM5-AS1 overexpression in cisplatin-resistant CC cells could induce the activation of the Hippo signaling pathway and the inactivation of the PI3K-AKT signaling pathway. PGM5-AS1 enhanced the CC cell's sensitivity to cisplatin by activating the Hippo signaling pathway and inactivating the PI3K-AKT signaling pathway. Our study data may provide a novel therapeutic biomarker to overcome cisplatin resistance in CC treatment.
{"title":"LncRNA PGM5-AS1 Impairs the Resistance of Cervical Cancer to Cisplatin by Regulating the Hippo and PI3K-AKT Pathways.","authors":"Huimin Wang, Yi Yang, Enjing Zhang, Dan Wang, Weiqiong Cai, Chun Li, Qiong Wei","doi":"10.1007/s10528-024-11011-0","DOIUrl":"https://doi.org/10.1007/s10528-024-11011-0","url":null,"abstract":"<p><p>Cisplatin, a platinum-based chemotherapeutic agent, can be used to treat cervical cancer (CC), but cisplatin resistance is increased during the cisplatin treatment. Long non-coding RNA PGM5-AS1 reportedly participates in CC tumorigenesis; however, its role in CC patients with cisplatin resistance has not been revealed. The present aimed to examine the role of PGM5-AS1 in modulating cisplatin resistance in CC. The PGM5-AS1 expression in CC tissues from 29 patients was quantified using quantitative reverse transcription-polymerase chain reaction. The cisplatin-resistant CC cells were constructed by using increasing cisplatin concentrations. The effects of cisplatin resistance interacting with PGM5-AS1 on CC cell malignancy were confirmed by performing Cell Counting Kit 8, colony formation, wound healing, and transwell assays. The key proteins of the Hippo and PI3K-AKT signaling pathways were evaluated by Western blotting. PGM5-AS1 with low expression in CC tissues was correlated to higher International Federation of Gynecology and Obstetrics stage, poor differentiation, lymph node metastasis, and cisplatin resistance. PGM5-AS1 overexpression suppressed the proliferation, migration, and invasion abilities of cisplatin-resistant CC cells. Additionally, PGM5-AS1 overexpression in cisplatin-resistant CC cells could induce the activation of the Hippo signaling pathway and the inactivation of the PI3K-AKT signaling pathway. PGM5-AS1 enhanced the CC cell's sensitivity to cisplatin by activating the Hippo signaling pathway and inactivating the PI3K-AKT signaling pathway. Our study data may provide a novel therapeutic biomarker to overcome cisplatin resistance in CC treatment.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-27DOI: 10.1007/s10528-024-11008-9
Jun Fang, Qiong Zhang, Qingrui Wang
Gastric cancer is associated with high morbidity and mortality rates and seriously threatens human life. Our research aimed to explore the effects of poly (A) binding protein cytoplasmic 1 (PABPC1) on gastric cancer cells and elucidate the underlying mechanisms.
Methods: PABPC1 levels in gastric cancer cell lines were assessed by western blotting and RT-qPCR. Cell viability, apoptosis, invasion, and migration were analyzed using MTT assay, flow cytometry, wound healing assay, and transwell assay, respectively. The levels of apoptosis-related proteins (caspase 3 and cleaved-caspase 3) were determined using the caspase 3 vitality test kit and western blotting. The levels of epithelial-to-mesenchymal transition-related genes (E-cadherin and N-cadherin) in AGS and MGC803 cells were analyzed using western blotting and RT-qPCR. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway was examined using western blot analysis.
Results: PABPC1 expression was enhanced in gastric cancer cells, especially in AGS and MGC803 cells. Our findings indicate that PABPC1 knockdown by siRNA inhibited PABPC1 expression, repressed gastric cancer cell growth, promoted apoptosis, and enhanced cleaved-caspase 3 expression. Functional assays revealed that PABPC1-siRNA blocked the migration and invasion of gastric cancer cells, dramatically promoted E-cadherin expression, and reduced N-cadherin levels. We also found decreased p-PI3K and p-AKT expression, along with decreased p-PI3K/PI3K and p-AKT/AKT in PABPC1-siRNA-treated gastric cancer cells.
Conclusion: PABPC1 silencing in gastric cancer cells inhibited cell proliferation, metastasis, and epithelial-to-mesenchymal transition, partly by repressing the PI3K/AKT signaling pathway activation. This may provide a theoretical basis for gastric cancer therapeutics.
{"title":"PABPC1 Silencing Inhibits Gastric Cancer Cell Proliferation, Metastasis, and EMT Via the PI3K/AKT Pathway.","authors":"Jun Fang, Qiong Zhang, Qingrui Wang","doi":"10.1007/s10528-024-11008-9","DOIUrl":"https://doi.org/10.1007/s10528-024-11008-9","url":null,"abstract":"<p><p>Gastric cancer is associated with high morbidity and mortality rates and seriously threatens human life. Our research aimed to explore the effects of poly (A) binding protein cytoplasmic 1 (PABPC1) on gastric cancer cells and elucidate the underlying mechanisms.</p><p><strong>Methods: </strong>PABPC1 levels in gastric cancer cell lines were assessed by western blotting and RT-qPCR. Cell viability, apoptosis, invasion, and migration were analyzed using MTT assay, flow cytometry, wound healing assay, and transwell assay, respectively. The levels of apoptosis-related proteins (caspase 3 and cleaved-caspase 3) were determined using the caspase 3 vitality test kit and western blotting. The levels of epithelial-to-mesenchymal transition-related genes (E-cadherin and N-cadherin) in AGS and MGC803 cells were analyzed using western blotting and RT-qPCR. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway was examined using western blot analysis.</p><p><strong>Results: </strong>PABPC1 expression was enhanced in gastric cancer cells, especially in AGS and MGC803 cells. Our findings indicate that PABPC1 knockdown by siRNA inhibited PABPC1 expression, repressed gastric cancer cell growth, promoted apoptosis, and enhanced cleaved-caspase 3 expression. Functional assays revealed that PABPC1-siRNA blocked the migration and invasion of gastric cancer cells, dramatically promoted E-cadherin expression, and reduced N-cadherin levels. We also found decreased p-PI3K and p-AKT expression, along with decreased p-PI3K/PI3K and p-AKT/AKT in PABPC1-siRNA-treated gastric cancer cells.</p><p><strong>Conclusion: </strong>PABPC1 silencing in gastric cancer cells inhibited cell proliferation, metastasis, and epithelial-to-mesenchymal transition, partly by repressing the PI3K/AKT signaling pathway activation. This may provide a theoretical basis for gastric cancer therapeutics.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-26DOI: 10.1007/s10528-024-11004-z
Yifei Weng, Guomin Xie
Alzheimer's disease (AD) and mild cognitive impairment (MCI) are a serious global public health problem. The aim of this study was to analyze the key molecular pathological mechanisms that occur in early AD progression as well as MCI. Expression profiling data from brain homogenates of 8 normal volunteers, and 6 patients with prodromal AD who had developed MCI were analyzed, and the data were obtained from GSE12685. Further, overexpression of GABBR2 was achieved in human neuroblastoma cell lines SH-SY5Y and BE(2)-M17 using expression plasmid transfection. GABBR2 was significantly overexpressed in brain tissues of patients with prodromal AD who had developed MCI, as compared to normal brains. Moreover, GABBR2 overexpressing cells showed a significant increase in intracellular Ca2+ concentration, a large amount of reactive oxygen species production, a large opening of the mitochondrial permeability transition pore and a significant increase in apoptosis compared with control cells. GABBR2 overexpression was significantly involved in early AD progression and MCI by causing cellular events such as intracellular Ca2+ imbalance, oxidative stress, and mitochondrial dysfunction.
{"title":"Increased GABBR2 Expression on Cell Membranes Causes Increased Ca2 + Inward Flow, Associated with Cognitive Impairment in Early Alzheimer's Disease.","authors":"Yifei Weng, Guomin Xie","doi":"10.1007/s10528-024-11004-z","DOIUrl":"https://doi.org/10.1007/s10528-024-11004-z","url":null,"abstract":"<p><p>Alzheimer's disease (AD) and mild cognitive impairment (MCI) are a serious global public health problem. The aim of this study was to analyze the key molecular pathological mechanisms that occur in early AD progression as well as MCI. Expression profiling data from brain homogenates of 8 normal volunteers, and 6 patients with prodromal AD who had developed MCI were analyzed, and the data were obtained from GSE12685. Further, overexpression of GABBR2 was achieved in human neuroblastoma cell lines SH-SY5Y and BE(2)-M17 using expression plasmid transfection. GABBR2 was significantly overexpressed in brain tissues of patients with prodromal AD who had developed MCI, as compared to normal brains. Moreover, GABBR2 overexpressing cells showed a significant increase in intracellular Ca<sup>2+</sup> concentration, a large amount of reactive oxygen species production, a large opening of the mitochondrial permeability transition pore and a significant increase in apoptosis compared with control cells. GABBR2 overexpression was significantly involved in early AD progression and MCI by causing cellular events such as intracellular Ca<sup>2+</sup> imbalance, oxidative stress, and mitochondrial dysfunction.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pulmonary hypertension (PH) is a progressive disease characterized by vascular reHypoxiaing, endothelial cell dysfunction, and inflammation. Liver Kinase B1 (LKB1, also known as STK11) is a central regulator of cell polarity and energy homeostasis. However, its specific role and mechanism of action in PH remain unclear. Human pulmonary arterial endothelial cells (hPAECs) were cultured in vitro to establish PH cell Hypoxias under normoxic and hypoxic conditions. The expression of LKB1 was detected by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) and western blotting, and its effect on hPAECs function was investigated by overexpression and inhibition of LKB1. Furthermore, cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, apoptosis was measured by flow cytometry, inflammatory cytokine secretion was evaluated using enzyme-linked immunosorbent assay (ELISA), and the expression of AMP-activated protein kinase (AMPK) signaling pathway-related proteins was analyzed by western blotting. LKB1 expression was significantly reduced in hypoxia-treated hPAECs compared with that in normoxic controls, and LKB1 overexpression significantly ameliorated the hypoxia-induced decrease in cell proliferation and increase in apoptosis as well as inflammatory factor secretion. The AMPK agonist (GSK621) reversed the dysfunction caused by LKB1 inhibition, indicating that LKB1 regulates hPAECs function through the AMPK signaling pathway. LKB1 plays a protective role in PH by inhibiting hPAECs dysfunction via activation of the AMPK pathway.
{"title":"Liver Kinase B1 Protects Against Hypoxia-Induced Pulmonary Arterial Endothelial Cell Dysfunction via the AMP-Activated Protein Kinase Pathway.","authors":"Bingchang Hei, Anzhe Zhang, Meiming Yang, Yunfei Jiang, Zhanjiang Guan","doi":"10.1007/s10528-024-11007-w","DOIUrl":"https://doi.org/10.1007/s10528-024-11007-w","url":null,"abstract":"<p><p>Pulmonary hypertension (PH) is a progressive disease characterized by vascular reHypoxiaing, endothelial cell dysfunction, and inflammation. Liver Kinase B1 (LKB1, also known as STK11) is a central regulator of cell polarity and energy homeostasis. However, its specific role and mechanism of action in PH remain unclear. Human pulmonary arterial endothelial cells (hPAECs) were cultured in vitro to establish PH cell Hypoxias under normoxic and hypoxic conditions. The expression of LKB1 was detected by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) and western blotting, and its effect on hPAECs function was investigated by overexpression and inhibition of LKB1. Furthermore, cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, apoptosis was measured by flow cytometry, inflammatory cytokine secretion was evaluated using enzyme-linked immunosorbent assay (ELISA), and the expression of AMP-activated protein kinase (AMPK) signaling pathway-related proteins was analyzed by western blotting. LKB1 expression was significantly reduced in hypoxia-treated hPAECs compared with that in normoxic controls, and LKB1 overexpression significantly ameliorated the hypoxia-induced decrease in cell proliferation and increase in apoptosis as well as inflammatory factor secretion. The AMPK agonist (GSK621) reversed the dysfunction caused by LKB1 inhibition, indicating that LKB1 regulates hPAECs function through the AMPK signaling pathway. LKB1 plays a protective role in PH by inhibiting hPAECs dysfunction via activation of the AMPK pathway.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-24DOI: 10.1007/s10528-024-10997-x
Enwa Felix Oghenemaro, Abdulrahman Qais Khaleel, Jasur Alimdjanovich Rizaev, R. Roopashree, Muath Suliman, Syeda Wajida Kazmi, Ahmed Hjazi, Pranchal Rajput, Yasser Fakri Mustafa, Munther Kadhim Abosaoda
The long non-coding RNA Growth Arrest-Specific 5 (GAS5) is pivotal in modulating key signaling pathways by functioning as a molecular sponge for microRNAs (miRNAs). GAS5 is notably recognized for its antitumor properties, primarily through its ability to sequester oncogenic miRNAs, thereby influencing critical pathways such as p53, Wnt/β-catenin, and PI3K/Akt, all of which are integral to cell proliferation, apoptosis, and metastasis. The disruption of GAS5–miRNA interactions has been implicated in various malignancies, reinforcing its potential as both a biomarker and a therapeutic target. This paper delves into the intricate signaling cascades affected by GAS5–miRNA interactions and thoroughly investigates the diagnosis and treatment prospects associated with GAS5. Moreover, it addresses both the challenges and opportunities for translational applicability of these findings in clinical environments. The study emphasizes GAS5’s significance within the cancer molecular landscape and posits that precise modulation of GAS5–miRNA interactions could catalyze transformative developments in cancer diagnostics and therapeutic approaches. This comprehensive review not only highlights the critical role of non-coding RNAs in cancer biology but also aims to lay the groundwork for future investigations aimed at harnessing these insights for therapeutic interventions.
{"title":"Dysregulation of GAS5–miRNA-Mediated Signaling Pathways in Cancer Pathobiology: A Comprehensive Exploration of Pathways Influenced by this Axis","authors":"Enwa Felix Oghenemaro, Abdulrahman Qais Khaleel, Jasur Alimdjanovich Rizaev, R. Roopashree, Muath Suliman, Syeda Wajida Kazmi, Ahmed Hjazi, Pranchal Rajput, Yasser Fakri Mustafa, Munther Kadhim Abosaoda","doi":"10.1007/s10528-024-10997-x","DOIUrl":"10.1007/s10528-024-10997-x","url":null,"abstract":"<div><p>The long non-coding RNA Growth Arrest-Specific 5 (GAS5) is pivotal in modulating key signaling pathways by functioning as a molecular sponge for microRNAs (miRNAs). GAS5 is notably recognized for its antitumor properties, primarily through its ability to sequester oncogenic miRNAs, thereby influencing critical pathways such as p53, Wnt/β-catenin, and PI3K/Akt, all of which are integral to cell proliferation, apoptosis, and metastasis. The disruption of GAS5–miRNA interactions has been implicated in various malignancies, reinforcing its potential as both a biomarker and a therapeutic target. This paper delves into the intricate signaling cascades affected by GAS5–miRNA interactions and thoroughly investigates the diagnosis and treatment prospects associated with GAS5. Moreover, it addresses both the challenges and opportunities for translational applicability of these findings in clinical environments. The study emphasizes GAS5’s significance within the cancer molecular landscape and posits that precise modulation of GAS5–miRNA interactions could catalyze transformative developments in cancer diagnostics and therapeutic approaches. This comprehensive review not only highlights the critical role of non-coding RNAs in cancer biology but also aims to lay the groundwork for future investigations aimed at harnessing these insights for therapeutic interventions.</p></div>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":"63 2","pages":"1149 - 1175"},"PeriodicalIF":2.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-24DOI: 10.1007/s10528-024-10985-1
Shuwei Bai, Haiyan Wang, Ye Bai, Peiyang Liu, Chunchao Bi
Retinoblastoma (RB) is an aggressive form of eye cancer. β-Asarone is a bioactive component isolated from the medicinal plant Acorus tatarinowii Schott and has anticancer effects on various human cancers. However, reports regarding the role of β-Asarone in RB remain limited. Our study investigates the mechanisms of β-Asarone in regulating drug resistance in RB, providing a theoretical foundation for RB treatment. A carboplatin-resistant RB cell line was established and treated with β-Asarone, followed by overexpression of long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1). The half-maximal inhibitory concentration and cell apoptosis were determined. The levels of lncRNA UCA1/miR-206/neuropilin 1 (NRP1) were measured. The subcellular localization of lncRNA UCA1 was examined. The binding relationships between lncRNA UCA1 and microRNA (miR)-206, and between miR-206 and NRP1 were analyzed. NRP1 expression was analyzed by Western blot assay. We found that β-Asarone downregulated lncRNA UCA1 expression in carboplatin-resistant RB cells. Overexpression of lncRNA UCA1 reversed the inhibitory effect of β-Asarone on cell drug resistance and cell proliferation and reduced apoptosis. LncRNA UCA1 functioned as a sponge for miR-206, which suppressed NRP1 expression. Inhibition of miR-206 or overexpression of NRP1 could partially reverse the suppressive effect of β-Asarone on RB cell drug resistance. In conclusion, β-Asarone suppresses RB cell drug resistance through the lncRNA UCA1/miR-206/NRP1 axis.
{"title":"β-Asarone Inhibits Carboplatin Resistance in Retinoblastoma Cells Through the UCA1/miR-206/NRP1 Axis.","authors":"Shuwei Bai, Haiyan Wang, Ye Bai, Peiyang Liu, Chunchao Bi","doi":"10.1007/s10528-024-10985-1","DOIUrl":"https://doi.org/10.1007/s10528-024-10985-1","url":null,"abstract":"<p><p>Retinoblastoma (RB) is an aggressive form of eye cancer. β-Asarone is a bioactive component isolated from the medicinal plant Acorus tatarinowii Schott and has anticancer effects on various human cancers. However, reports regarding the role of β-Asarone in RB remain limited. Our study investigates the mechanisms of β-Asarone in regulating drug resistance in RB, providing a theoretical foundation for RB treatment. A carboplatin-resistant RB cell line was established and treated with β-Asarone, followed by overexpression of long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1). The half-maximal inhibitory concentration and cell apoptosis were determined. The levels of lncRNA UCA1/miR-206/neuropilin 1 (NRP1) were measured. The subcellular localization of lncRNA UCA1 was examined. The binding relationships between lncRNA UCA1 and microRNA (miR)-206, and between miR-206 and NRP1 were analyzed. NRP1 expression was analyzed by Western blot assay. We found that β-Asarone downregulated lncRNA UCA1 expression in carboplatin-resistant RB cells. Overexpression of lncRNA UCA1 reversed the inhibitory effect of β-Asarone on cell drug resistance and cell proliferation and reduced apoptosis. LncRNA UCA1 functioned as a sponge for miR-206, which suppressed NRP1 expression. Inhibition of miR-206 or overexpression of NRP1 could partially reverse the suppressive effect of β-Asarone on RB cell drug resistance. In conclusion, β-Asarone suppresses RB cell drug resistance through the lncRNA UCA1/miR-206/NRP1 axis.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-23DOI: 10.1007/s10528-024-10965-5
Haitham Saleh, Abdelfattah Badr, Ehab M Zayed, Elham R S Soliman
Pearl millet {Pennisetum glaucum (L.) R. Br} is a C4 panicoid cereal millet crop grown in arid and semi-arid regions in Africa and Asia for food and fodder. This study involves the evaluation of the genetic diversity of 28 worldwide germplasm collection of pearl millet by genetic markers polymorphism and drought tolerance indices. The genetic diversity was expressed by 51 alleles of 9 ISSR markers that showed 96.43% total polymorphism and 11.76 alleles per marker. Cluster analysis of ISSR markers polymorphism divided the 28 genotypes into four clusters partially in agreement with their origin. The application of drought stress simulated by 20% PEG6000 treatment, retarded the germination percentage, and reduced shoot and root length, seedling fresh and dry weights. Drought tolerance indices (DTIs) were calculated based on the response of the seedling traits under drought stress compared to the control seedlings. ANOVA revealed statistically significant variation among the genotypes (P ≤ 0.05), except for seedling fresh weight (P = 0.17 > 0.05) under control conditions and seedling dry weight (P = 0.99 > 0.05) under drought conditions. Genotypes having higher DTIs for three traits are regarded drought resistant, i.e., those from India, Ethiopia, Pakistan, and Nigeria. The calculated heritability values indicated that seedlings dry weight is the least trait affected by drought stress whereas root length is the most influenced trait. Hierarchical clustering, based on the DTI values, also grouped the genotypes partially concomitant to their origin. The correlation analysis demonstrated a modest positive correlation between shoot length and root length. A low correlation of r ≤ 0.12 was observed between the morphological DTI matrix and the genetic matrix. Nevertheless, high levels of genetic diversity were identified among the examined genotypes that may face genetic erosion by climatic constraints, and a high potential for creating agronomically superior cultivars by crossing widely divergent genotypes.
{"title":"Genetic Diversity and Drought Stress Tolerance of a Global Collection of Pearl Millet at Germination and Early Seedling Growth Stages.","authors":"Haitham Saleh, Abdelfattah Badr, Ehab M Zayed, Elham R S Soliman","doi":"10.1007/s10528-024-10965-5","DOIUrl":"https://doi.org/10.1007/s10528-024-10965-5","url":null,"abstract":"<p><p>Pearl millet {Pennisetum glaucum (L.) R. Br} is a C4 panicoid cereal millet crop grown in arid and semi-arid regions in Africa and Asia for food and fodder. This study involves the evaluation of the genetic diversity of 28 worldwide germplasm collection of pearl millet by genetic markers polymorphism and drought tolerance indices. The genetic diversity was expressed by 51 alleles of 9 ISSR markers that showed 96.43% total polymorphism and 11.76 alleles per marker. Cluster analysis of ISSR markers polymorphism divided the 28 genotypes into four clusters partially in agreement with their origin. The application of drought stress simulated by 20% PEG<sub>6000</sub> treatment, retarded the germination percentage, and reduced shoot and root length, seedling fresh and dry weights. Drought tolerance indices (DTIs) were calculated based on the response of the seedling traits under drought stress compared to the control seedlings. ANOVA revealed statistically significant variation among the genotypes (P ≤ 0.05), except for seedling fresh weight (P = 0.17 > 0.05) under control conditions and seedling dry weight (P = 0.99 > 0.05) under drought conditions. Genotypes having higher DTIs for three traits are regarded drought resistant, i.e., those from India, Ethiopia, Pakistan, and Nigeria. The calculated heritability values indicated that seedlings dry weight is the least trait affected by drought stress whereas root length is the most influenced trait. Hierarchical clustering, based on the DTI values, also grouped the genotypes partially concomitant to their origin. The correlation analysis demonstrated a modest positive correlation between shoot length and root length. A low correlation of r ≤ 0.12 was observed between the morphological DTI matrix and the genetic matrix. Nevertheless, high levels of genetic diversity were identified among the examined genotypes that may face genetic erosion by climatic constraints, and a high potential for creating agronomically superior cultivars by crossing widely divergent genotypes.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}