Yu-Long Hu, Fang Yang, Yan-Tong Chen, Shuo-Kai Shen, Yu-Bo Yan, Yue-Bo Zhang, Xiao-Lin Wu, Jia-Ming Wang, Jun He, Ning Gao
Genomic prediction has emerged as a pivotal technology for the genetic evaluation of livestock, crops, and for predicting human disease risks. However, classical genomic prediction methods face challenges in incorporating biological prior information such as the genetic regulation mechanisms of traits. This study introduces a novel approach that integrates mRNA transcript information to predict complex trait phenotypes. To evaluate the accuracy of the new method, we utilized a Drosophila population that is widely employed in quantitative genetics researches globally. Results indicate that integrating mRNA transcript data can significantly enhance the genomic prediction accuracy for certain traits, though it does not improve phenotype prediction accuracy for all traits. Compared with GBLUP, the prediction accuracy for olfactory response to dCarvone in male Drosophila increased from 0.256 to 0.274. Similarly, the accuracy for cafe in male Drosophila rose from 0.355 to 0.401. The prediction accuracy for survival_paraquat in male Drosophila is improved from 0.101 to 0.138. In female Drosophila, the accuracy of olfactory response to 1hexanol increased from 0.147 to 0.210. In conclusion, integrating mRNA transcripts can substantially improve genomic prediction accuracy of certain traits by up to 43%, with range of 7% to 43%. Furthermore, for some traits, considering interaction effects along with mRNA transcript integration can lead to even higher prediction accuracy.
{"title":"Integrating mRNA transcripts and genomic information into genomic prediction.","authors":"Yu-Long Hu, Fang Yang, Yan-Tong Chen, Shuo-Kai Shen, Yu-Bo Yan, Yue-Bo Zhang, Xiao-Lin Wu, Jia-Ming Wang, Jun He, Ning Gao","doi":"10.16288/j.yczz.24-096","DOIUrl":"https://doi.org/10.16288/j.yczz.24-096","url":null,"abstract":"<p><p>Genomic prediction has emerged as a pivotal technology for the genetic evaluation of livestock, crops, and for predicting human disease risks. However, classical genomic prediction methods face challenges in incorporating biological prior information such as the genetic regulation mechanisms of traits. This study introduces a novel approach that integrates mRNA transcript information to predict complex trait phenotypes. To evaluate the accuracy of the new method, we utilized a <i>Drosophila</i> population that is widely employed in quantitative genetics researches globally. Results indicate that integrating mRNA transcript data can significantly enhance the genomic prediction accuracy for certain traits, though it does not improve phenotype prediction accuracy for all traits. Compared with GBLUP, the prediction accuracy for olfactory response to dCarvone in male <i>Drosophila</i> increased from 0.256 to 0.274. Similarly, the accuracy for cafe in male <i>Drosophila</i> rose from 0.355 to 0.401. The prediction accuracy for survival_paraquat in male <i>Drosophila</i> is improved from 0.101 to 0.138. In female <i>Drosophila</i>, the accuracy of olfactory response to 1hexanol increased from 0.147 to 0.210. In conclusion, integrating mRNA transcripts can substantially improve genomic prediction accuracy of certain traits by up to 43%, with range of 7% to 43%. Furthermore, for some traits, considering interaction effects along with mRNA transcript integration can lead to even higher prediction accuracy.</p>","PeriodicalId":35536,"journal":{"name":"Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji","volume":"46 7","pages":"560-569"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Accurate breed classification is required for the conservation and utilization of farm animal genetic resources. Traditional classification methods mainly rely on phenotypic characterization. However, it is difficult to distinguish between the highly similar breeds due to the challenges in qualifying the phenotypic character. Machine learning algorithms show unique advantages in breed classification using genomic information. To evaluate the classification methods for Chinese cattle breeds, this study utilized genomic SNP data from 213 individuals across seven Chinese local breeds and compared the classification accuracies of three feature selection methods (FST value sorting and screening, mRMR, and Relief-F) and three machine learning algorithms (Random Forest, Support Vector Machine, and Naive Bayes). Results showed that: 1) using the FST method to screen more than 1500 SNPs, or using the mRMR algorithm to screen more than 1000 SNPs, the SVM classification algorithm can achieve more than 99.47% classification accuracy; 2) the most effective algorithm was SVM, followed by NB, while the best SNP selection method was FST and mRMR, followed by Relief-F; 3) species misclassification often occurs between breeds with high similarity. This study demonstrates that machine learning classification models combined with genomic data are effective methods for the classification of local cattle breeds, providing a technical basis for the rapid and accurate classification of cattle breeds in China.
{"title":"Classification accuracy of machine learning algorithms for Chinese local cattle breeds using genomic markers.","authors":"Hui Liang, Xue Wang, Jing-Fang Si, Yi Zhang","doi":"10.16288/j.yczz.24-059","DOIUrl":"https://doi.org/10.16288/j.yczz.24-059","url":null,"abstract":"<p><p>Accurate breed classification is required for the conservation and utilization of farm animal genetic resources. Traditional classification methods mainly rely on phenotypic characterization. However, it is difficult to distinguish between the highly similar breeds due to the challenges in qualifying the phenotypic character. Machine learning algorithms show unique advantages in breed classification using genomic information. To evaluate the classification methods for Chinese cattle breeds, this study utilized genomic SNP data from 213 individuals across seven Chinese local breeds and compared the classification accuracies of three feature selection methods (F<sub>ST</sub> value sorting and screening, mRMR, and Relief-F) and three machine learning algorithms (Random Forest, Support Vector Machine, and Naive Bayes). Results showed that: 1) using the F<sub>ST</sub> method to screen more than 1500 SNPs, or using the mRMR algorithm to screen more than 1000 SNPs, the SVM classification algorithm can achieve more than 99.47% classification accuracy; 2) the most effective algorithm was SVM, followed by NB, while the best SNP selection method was F<sub>ST</sub> and mRMR, followed by Relief-F; 3) species misclassification often occurs between breeds with high similarity. This study demonstrates that machine learning classification models combined with genomic data are effective methods for the classification of local cattle breeds, providing a technical basis for the rapid and accurate classification of cattle breeds in China.</p>","PeriodicalId":35536,"journal":{"name":"Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji","volume":"46 7","pages":"530-539"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biodiversity losses along with the exponential growth of global human population and human-provoked over-exploitation of natural resources. Genetic factors played an important role in the conservation of endangered species. Conservation genetics is a cross-field disciplinary of genetics and conservation biology. The course of conservation genetics is not available in colleges and universities, and the course of genetics does not directly reflect the content of biological conservation. We have taught genetics with integrative thoughts of conservation biology. In the form of case studies, we have integrated recent advances of research and technology in the relevant fields into the genetics classroom. As a result, we improved the undergraduates' motivation and interest in active learning, provoked the mutual promotion of "basic knowledge of genetics, awareness of ecological protection, and cultivate interdisciplinary thinking", and set up the groundwork for cultivating interdisciplinary talents who not only master solid basic knowledge, but also have the concept of ecological civilization.
{"title":"Teaching genetics with integrative thoughts of conservation biology.","authors":"Jian-Qing Lin, Shao-Pan Ye, Shu-Qi Wang, Hong Du","doi":"10.16288/j.yczz.24-127","DOIUrl":"https://doi.org/10.16288/j.yczz.24-127","url":null,"abstract":"<p><p>Biodiversity losses along with the exponential growth of global human population and human-provoked over-exploitation of natural resources. Genetic factors played an important role in the conservation of endangered species. Conservation genetics is a cross-field disciplinary of genetics and conservation biology. The course of conservation genetics is not available in colleges and universities, and the course of genetics does not directly reflect the content of biological conservation. We have taught genetics with integrative thoughts of conservation biology. In the form of case studies, we have integrated recent advances of research and technology in the relevant fields into the genetics classroom. As a result, we improved the undergraduates' motivation and interest in active learning, provoked the mutual promotion of \"basic knowledge of genetics, awareness of ecological protection, and cultivate interdisciplinary thinking\", and set up the groundwork for cultivating interdisciplinary talents who not only master solid basic knowledge, but also have the concept of ecological civilization.</p>","PeriodicalId":35536,"journal":{"name":"Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji","volume":"46 7","pages":"581-586"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sperm chromatin not only carries genetic information such as paternal DNA, but also carries structural proteins, epigenetic information, and higher-order chromatin structures (such as matrix attachment regions and telomeres), etc. These information play an important role in embryonic development. This article mainly reviews the effects of these different information carried by sperm chromatin on sperm function and embryonic development and the research progress of related detection methods, in order to provide a theoretical basis and scientific diagnosis and treatment strategies for the etiology screening of clinical infertility, embryo arrest and recurrent miscarriage, so as to improve the pregnancy outcomes of natural conception and assisted reproduction. Keywords: sperm chromatin; epigenetics; sperm DNA damage; sperm function; higher-order chromatin structures.
精子染色质不仅携带父系 DNA 等遗传信息,还携带结构蛋白、表观遗传信息和高阶染色质结构(如基质附着区和端粒)等。这些信息在胚胎发育过程中发挥着重要作用。本文主要综述了精子染色质所携带的这些不同信息对精子功能和胚胎发育的影响以及相关检测方法的研究进展,以期为临床不孕症、胚胎停育和复发性流产的病因筛查提供理论依据和科学的诊治策略,从而提高自然受孕和辅助生殖的妊娠结局。关键词:精子染色质;表观遗传学;精子DNA损伤;精子功能;高阶染色质结构。
{"title":"Research progress on the effect of sperm chromatin integrity on function and its detection methods.","authors":"Daiyuan Liu, Zhao-Hui Zhang, Xian-Jiang Kang","doi":"10.16288/j.yczz.24-106","DOIUrl":"https://doi.org/10.16288/j.yczz.24-106","url":null,"abstract":"<p><p>Sperm chromatin not only carries genetic information such as paternal DNA, but also carries structural proteins, epigenetic information, and higher-order chromatin structures (such as matrix attachment regions and telomeres), etc. These information play an important role in embryonic development. This article mainly reviews the effects of these different information carried by sperm chromatin on sperm function and embryonic development and the research progress of related detection methods, in order to provide a theoretical basis and scientific diagnosis and treatment strategies for the etiology screening of clinical infertility, embryo arrest and recurrent miscarriage, so as to improve the pregnancy outcomes of natural conception and assisted reproduction. Keywords: sperm chromatin; epigenetics; sperm DNA damage; sperm function; higher-order chromatin structures.</p>","PeriodicalId":35536,"journal":{"name":"Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji","volume":"46 7","pages":"511-529"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Duchenne muscular dystrophy (DMD) is a severe X-linked recessive genetic disorder caused by mutations in the DMD gene, which leads to a deficiency of the dystrophin protein. The main mutation types of this gene include exon deletions and duplications, point mutations, and insertions. These mutations disrupt the normal expression of dystrophin, ultimately leading to the disease. In this study, we reported a case of DMD caused by an insertion mutation in exon 59 (E59) of the DMD gene. The affected child exhibited significant abnormalities in related biochemical markers, early symptoms of DMD, and multiple gray hair. His mother and sister were carriers with slightly abnormal biochemical markers. The mother had mild clinical symptoms, while the sister had no clinical symptoms. Other family members were genetically and physically normal. Sequencing and sequence alignment revealed that the inserted fragment was an Alu element from the AluYa5 subfamily. This insertion produced two stop codons and a polyadenylate (polyA) tail. To understand the impact of this insertion on the DMD gene and its association with clinical symptoms, exonic splicing enhancer (ESE) prediction indicated that the insertion did not affect the splicing of E59. Therefore, we speculated that the insertion sequence would be present in the mRNA sequence of the DMD gene. The two stop codons and polyA tail likely terminate translation, preventing the production of functional dystrophin protein, which may be the mechanism leading to DMD. In addition to typical DMD symptoms, the child also exhibited premature graying of hair. This study reports, for the first time, a case of DMD caused by the insertion of an Alu element into the coding region of the DMD gene. This finding provides clues for studying gene mutations induced by Alu sequence insertion and expands the understanding of DMD gene mutations.
杜兴氏肌营养不良症(DMD)是一种严重的 X 连锁隐性遗传疾病,由 DMD 基因突变引起,导致肌营养蛋白缺乏。该基因的主要突变类型包括外显子缺失和重复、点突变和插入。这些突变会破坏肌营养不良蛋白的正常表达,最终导致该病。在这项研究中,我们报告了一例由 DMD 基因 59 号外显子(E59)插入突变引起的 DMD 病例。患儿表现出相关生化指标的明显异常、DMD 的早期症状和多根白发。他的母亲和姐姐是生化指标轻微异常的携带者。母亲有轻微的临床症状,而姐姐则没有临床症状。其他家庭成员的基因和身体状况正常。测序和序列比对显示,插入的片段是一个来自 AluYa5 亚家族的 Alu 元件。该插入片段产生了两个终止密码子和一个多聚腺苷酸(polyA)尾。为了了解该插入片段对 DMD 基因的影响及其与临床症状的关系,我们对外显子剪接增强子(ESE)进行了预测,结果表明该插入片段并不影响 E59 的剪接。因此,我们推测插入序列可能存在于 DMD 基因的 mRNA 序列中。两个终止密码子和 polyA 尾部可能会终止翻译,从而阻止产生功能性肌营养不良蛋白,这可能是导致 DMD 的机制。除了典型的 DMD 症状外,该患儿还表现出头发过早变白。本研究首次报告了一例因在 DMD 基因编码区插入 Alu 元素而导致的 DMD 病例。这一发现为研究 Alu 序列插入诱导的基因突变提供了线索,并拓展了人们对 DMD 基因突变的认识。
{"title":"A case study of Duchenne muscular dystrophy caused by Alu element insertion in <i>DMD</i> gene and analysis of its gray-hair symptoms.","authors":"Hui Li, Ru-Yi Zhang, Chang-Ye Li, Xiao-Lin Zhang, Qing-Yin Zheng, Xiu-Zhen Liu","doi":"10.16288/j.yczz.24-020","DOIUrl":"10.16288/j.yczz.24-020","url":null,"abstract":"<p><p>Duchenne muscular dystrophy (DMD) is a severe X-linked recessive genetic disorder caused by mutations in the <i>DMD</i> gene, which leads to a deficiency of the dystrophin protein. The main mutation types of this gene include exon deletions and duplications, point mutations, and insertions. These mutations disrupt the normal expression of dystrophin, ultimately leading to the disease. In this study, we reported a case of DMD caused by an insertion mutation in exon 59 (E59) of the <i>DMD</i> gene. The affected child exhibited significant abnormalities in related biochemical markers, early symptoms of DMD, and multiple gray hair. His mother and sister were carriers with slightly abnormal biochemical markers. The mother had mild clinical symptoms, while the sister had no clinical symptoms. Other family members were genetically and physically normal. Sequencing and sequence alignment revealed that the inserted fragment was an Alu element from the AluYa5 subfamily. This insertion produced two stop codons and a polyadenylate (polyA) tail. To understand the impact of this insertion on the <i>DMD</i> gene and its association with clinical symptoms, exonic splicing enhancer (ESE) prediction indicated that the insertion did not affect the splicing of E59. Therefore, we speculated that the insertion sequence would be present in the mRNA sequence of the <i>DMD</i> gene. The two stop codons and polyA tail likely terminate translation, preventing the production of functional dystrophin protein, which may be the mechanism leading to DMD. In addition to typical DMD symptoms, the child also exhibited premature graying of hair. This study reports, for the first time, a case of DMD caused by the insertion of an Alu element into the coding region of the <i>DMD</i> gene. This finding provides clues for studying gene mutations induced by Alu sequence insertion and expands the understanding of <i>DMD</i> gene mutations.</p>","PeriodicalId":35536,"journal":{"name":"Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji","volume":"46 7","pages":"570-580"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
During meiosis, defects in cohesin localization within the centromere region can result in various diseases. Accurate cohesin localization depends on the Mis4-Ssl3 loading complex. Although it is known that cohesin completes the loading process with the help of the loading complex, the mechanisms underlying its localization in the centromere region remain unclear. Previous studies suggest cohesin localization in the centromere is mediated by phosphorylation of centromeric proteins. In this study, we focused on the Fta2 protein, a component of the Sim4 centromere protein complex. Using bioinformatics methods, potential phosphorylation sites were identified, and fta2-9A and fta2-9D mutants were constructed in Schizosaccharomyces pombe. The phenotypes of these mutants were characterized through testing thiabendazole (TBZ) sensitivity and fluorescent microscopy localization. Results indicated that Fta2 phosphorylation did not impact mitosis but affected chromosome segregation during meiosis. This study suggests that Fta2 phosphorylation is vital for meiosis and may be related to the specific localization of cohesin during this process.
{"title":"The effect of centromere protein Fta2 phosphorylation during meiosis.","authors":"Zi-Han Ni, Yu Min, Ling-Ling Ma, Yoshinori Watanabe","doi":"10.16288/j.yczz.24-038","DOIUrl":"10.16288/j.yczz.24-038","url":null,"abstract":"<p><p>During meiosis, defects in cohesin localization within the centromere region can result in various diseases. Accurate cohesin localization depends on the Mis4-Ssl3 loading complex. Although it is known that cohesin completes the loading process with the help of the loading complex, the mechanisms underlying its localization in the centromere region remain unclear. Previous studies suggest cohesin localization in the centromere is mediated by phosphorylation of centromeric proteins. In this study, we focused on the Fta2 protein, a component of the Sim4 centromere protein complex. Using bioinformatics methods, potential phosphorylation sites were identified, and <i>fta2-9A</i> and <i>fta2-9D</i> mutants were constructed in <i>Schizosaccharomyces pombe</i>. The phenotypes of these mutants were characterized through testing thiabendazole (TBZ) sensitivity and fluorescent microscopy localization. Results indicated that Fta2 phosphorylation did not impact mitosis but affected chromosome segregation during meiosis. This study suggests that Fta2 phosphorylation is vital for meiosis and may be related to the specific localization of cohesin during this process.</p>","PeriodicalId":35536,"journal":{"name":"Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji","volume":"46 7","pages":"552-559"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Metronidazole (MTZ), a commonly used anti-infective drug in clinical practice, has also been employed as a prodrug in cell-targeted ablation systems in scientific research, exhibiting significant application value. However, it has been demonstrated that MTZ can induce neurotoxic symptoms to some extent during its use, and there is currently a lack of effective means to circumvent its toxicity in both clinical and research settings, which limits its application. Therefore, exploring the specific mechanisms underlying MTZ-induced neurotoxic symptoms and elucidating countermeasures will enhance the practical value of MTZ. In this study, using a zebrafish spinal cord injury regeneration model, we confirmed that MTZ neurotoxicity leads to impaired axon regeneration in the central nervous system. By overexpressing il34 in the central nervous system of zebrafish, we eliminated the inhibitory effect of MTZ on axonal regeneration and demonstrated that the pro-regenerative effect against MTZ neurotoxicity is not caused by excessive macrophages/microglia chemoattracted by interleukin 34(Il34). Transcriptome sequencing analysis and GO enrichment analysis of differentially expressed genes between groups revealed that Il34 may counteract MTZ neurotoxicity and promote spinal cord injury repair through biological processes that enhance cellular adhesion and cell location. In summary, our work uncovers a possible cause of MTZ neurotoxicity and provides a new perspective for eliminating MTZ toxicity.
{"title":"Il34 rescues metronidazole-induced impairment of spinal cord regeneration in zebrafish central nervous system.","authors":"Ji-Xiang Liu, Si-Ting Lai, Jing Bai, Jin Xu","doi":"10.16288/j.yczz.24-083","DOIUrl":"10.16288/j.yczz.24-083","url":null,"abstract":"<p><p>Metronidazole (MTZ), a commonly used anti-infective drug in clinical practice, has also been employed as a prodrug in cell-targeted ablation systems in scientific research, exhibiting significant application value. However, it has been demonstrated that MTZ can induce neurotoxic symptoms to some extent during its use, and there is currently a lack of effective means to circumvent its toxicity in both clinical and research settings, which limits its application. Therefore, exploring the specific mechanisms underlying MTZ-induced neurotoxic symptoms and elucidating countermeasures will enhance the practical value of MTZ. In this study, using a zebrafish spinal cord injury regeneration model, we confirmed that MTZ neurotoxicity leads to impaired axon regeneration in the central nervous system. By overexpressing <i>il34</i> in the central nervous system of zebrafish, we eliminated the inhibitory effect of MTZ on axonal regeneration and demonstrated that the pro-regenerative effect against MTZ neurotoxicity is not caused by excessive macrophages/microglia chemoattracted by interleukin 34(Il34). Transcriptome sequencing analysis and GO enrichment analysis of differentially expressed genes between groups revealed that Il34 may counteract MTZ neurotoxicity and promote spinal cord injury repair through biological processes that enhance cellular adhesion and cell location. In summary, our work uncovers a possible cause of MTZ neurotoxicity and provides a new perspective for eliminating MTZ toxicity.</p>","PeriodicalId":35536,"journal":{"name":"Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji","volume":"46 6","pages":"478-489"},"PeriodicalIF":0.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LIN28A and its homolog LIN28B are highly conserved RNA-binding proteins that play important roles in early embryonic development, somatic cell reprogramming, metabolism and tumorigenesis. LIN28A/B are highly expressed in a variety of malignant tumors such as breast cancer. They play important roles in the initiation, maintenance, and metastasis of tumors and are associated with poor prognosis. Previous studies have shown that the main regulatory mechanisms of LIN28A/B include let-7s dependent ways and let-7s independent ways, such as directly targeting mRNA. In this review, we summarize the function and molecular regulatory mechanisms of LIN28A/B in malignant tumors such as liver cancer, breast cancer and colorectal cancer, in order to provide references for further exploring the function and mechanism of LIN28A/B and their possible roles in clinical applications.
{"title":"Progress on the role of LIN28A/B in tumor development and progression.","authors":"Yi-Wen Zhang, Qin Huang, Yan-Yun Wu, Yue Sun, Yong-Long Wei","doi":"10.16288/j.yczz.24-056","DOIUrl":"10.16288/j.yczz.24-056","url":null,"abstract":"<p><p>LIN28A and its homolog LIN28B are highly conserved RNA-binding proteins that play important roles in early embryonic development, somatic cell reprogramming, metabolism and tumorigenesis. LIN28A/B are highly expressed in a variety of malignant tumors such as breast cancer. They play important roles in the initiation, maintenance, and metastasis of tumors and are associated with poor prognosis. Previous studies have shown that the main regulatory mechanisms of LIN28A/B include let-7s dependent ways and let-7s independent ways, such as directly targeting mRNA. In this review, we summarize the function and molecular regulatory mechanisms of LIN28A/B in malignant tumors such as liver cancer, breast cancer and colorectal cancer, in order to provide references for further exploring the function and mechanism of LIN28A/B and their possible roles in clinical applications.</p>","PeriodicalId":35536,"journal":{"name":"Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji","volume":"46 6","pages":"452-465"},"PeriodicalIF":0.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jian Yang, Guo-Juan Shi, Ang-Hui Peng, Qing-Bo Xu, Rui-Qi Wang, Lei Xue, Xin-Yang Yu, Yi-Hao Sun
The JNK signaling pathway plays crucial roles in various physiological processes, including cell proliferation, differentiation, migration, apoptosis, and stress response. Dysregulation of this pathway is closely linked to the onset and progression of numerous major diseases, such as developmental defects and tumors. Identifying and characterizing novel components of the JNK signaling pathway to enhance and refine its network hold significant scientific and clinical importance for the prevention and treatment of associated cancers. This study utilized the model organism Drosophila and employed multidisciplinary approaches encompassing genetics, developmental biology, biochemistry, and molecular biology to investigate the interplay between Tip60 and the JNK signaling pathway, and elucidated its regulatory mechanisms. Our findings suggest that loss of Tip60 acetyltransferase activity results in JNK signaling pathway activation and subsequent induction of JNK-dependent apoptosis. Genetic epistasis analysis reveals that Tip60 acts downstream of JNK, paralleling with the transcription factor FOXO. The biochemical results confirm that Tip60 can bind to FOXO and acetylate it. Introduction of human Tip60 into Drosophila effectively mitigates apoptosis induced by JNK signaling activation, underscoring conserved regulatory role of Tip60 in the JNK signaling pathway from Drosophila to humans. This study further enhances our understanding of the regulatory network of the JNK signaling pathway. By revealing the role and mechanism of Tip60 in JNK-dependent apoptosis, it unveils new insights and potential therapeutic avenues for preventing and treating associated cancers.
{"title":"Tip60-FOXO regulates JNK signaling mediated apoptosis in <i>Drosophila</i>.","authors":"Jian Yang, Guo-Juan Shi, Ang-Hui Peng, Qing-Bo Xu, Rui-Qi Wang, Lei Xue, Xin-Yang Yu, Yi-Hao Sun","doi":"10.16288/j.yczz.24-105","DOIUrl":"10.16288/j.yczz.24-105","url":null,"abstract":"<p><p>The JNK signaling pathway plays crucial roles in various physiological processes, including cell proliferation, differentiation, migration, apoptosis, and stress response. Dysregulation of this pathway is closely linked to the onset and progression of numerous major diseases, such as developmental defects and tumors. Identifying and characterizing novel components of the JNK signaling pathway to enhance and refine its network hold significant scientific and clinical importance for the prevention and treatment of associated cancers. This study utilized the model organism <i>Drosophila</i> and employed multidisciplinary approaches encompassing genetics, developmental biology, biochemistry, and molecular biology to investigate the interplay between Tip60 and the JNK signaling pathway, and elucidated its regulatory mechanisms. Our findings suggest that loss of Tip60 acetyltransferase activity results in JNK signaling pathway activation and subsequent induction of JNK-dependent apoptosis. Genetic epistasis analysis reveals that Tip60 acts downstream of JNK, paralleling with the transcription factor FOXO. The biochemical results confirm that Tip60 can bind to FOXO and acetylate it. Introduction of human Tip60 into <i>Drosophila</i> effectively mitigates apoptosis induced by JNK signaling activation, underscoring conserved regulatory role of Tip60 in the JNK signaling pathway from <i>Drosophila</i> to humans. This study further enhances our understanding of the regulatory network of the JNK signaling pathway. By revealing the role and mechanism of Tip60 in JNK-dependent apoptosis, it unveils new insights and potential therapeutic avenues for preventing and treating associated cancers.</p>","PeriodicalId":35536,"journal":{"name":"Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji","volume":"46 6","pages":"490-501"},"PeriodicalIF":0.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}