Functional & Integrative Genomics最新文献

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Ischemic cardiac stromal fibroblast-derived protein mediators in the infarcted myocardium and transcriptomic profiling at single cell resolution 缺血性心肌基质成纤维细胞衍生蛋白介质在梗死心肌中的作用以及单细胞分辨率的转录组分析。
IF 3.9 4区 生物学
Functional & Integrative Genomics Pub Date : 2024-09-20 DOI: 10.1007/s10142-024-01457-1
Ed Cha, Sung Ho Hong, Taj Rai, Vy La, Pranav Madabhushi, Darren Teramoto, Cameron Fung, Pauline Cheng, Yu Chen, Angelo Keklikian, Jeffrey Liu, William Fang, Finosh G. Thankam
{"title":"Ischemic cardiac stromal fibroblast-derived protein mediators in the infarcted myocardium and transcriptomic profiling at single cell resolution","authors":"Ed Cha,&nbsp;Sung Ho Hong,&nbsp;Taj Rai,&nbsp;Vy La,&nbsp;Pranav Madabhushi,&nbsp;Darren Teramoto,&nbsp;Cameron Fung,&nbsp;Pauline Cheng,&nbsp;Yu Chen,&nbsp;Angelo Keklikian,&nbsp;Jeffrey Liu,&nbsp;William Fang,&nbsp;Finosh G. Thankam","doi":"10.1007/s10142-024-01457-1","DOIUrl":"10.1007/s10142-024-01457-1","url":null,"abstract":"<div><p>This article focuses on screening the major secreted proteins by the ischemia-challenged cardiac stromal fibroblasts (CF), the assessment of their expression status and functional role in the post-ischemic left ventricle (LV) and in the ischemia-challenged CF culture and to phenotype CF at single cell resolution based on the positivity of the identified mediators. The expression level of CRSP2, HSP27, IL-8, Cofilin-1, and HSP90 in the LV tissues following coronary artery bypass graft (CABG) and myocardial infarction (MI) and CF cells followed the screening profile derived from the MS/MS findings. The histology data unveiled ECM disorganization, inflammation and fibrosis reflecting the ischemic pathology. CRSP2, HSP27, and HSP90 were significantly upregulated in the LV-CABG tissues with a concomitant reduction ion LV-MI whereas Cofilin-1, IL8, Nrf2, and Troponin I were downregulated in LV-CABG and increased in LV-MI. Similar trends were exhibited by ischemic CF. Single cell transcriptomics revealed multiple sub-phenotypes of CF based on their respective upregulation of CRSP2, HSP27, IL-8, Cofilin-1, HSP90, Troponin I and Nrf2 unveiling pathological and pro-healing phenotypes. Further investigations regarding the underlying signaling mechanisms and validation of sub-populations would offer novel translational avenues for the management of cardiac diseases.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
lncRNA HOTAIR and Cardiovascular diseases lncRNA HOTAIR 与心血管疾病
IF 3.9 4区 生物学
Functional & Integrative Genomics Pub Date : 2024-09-19 DOI: 10.1007/s10142-024-01444-6
Sina Taghvimi, Elahe Soltani Fard, Seyyed Hossein Khatami, Sara Zafaranchi Z. M., Mortaza Taheri-Anganeh, Ahmad Movahedpour, Hassan Ghasemi
{"title":"lncRNA HOTAIR and Cardiovascular diseases","authors":"Sina Taghvimi,&nbsp;Elahe Soltani Fard,&nbsp;Seyyed Hossein Khatami,&nbsp;Sara Zafaranchi Z. M.,&nbsp;Mortaza Taheri-Anganeh,&nbsp;Ahmad Movahedpour,&nbsp;Hassan Ghasemi","doi":"10.1007/s10142-024-01444-6","DOIUrl":"10.1007/s10142-024-01444-6","url":null,"abstract":"<div><p>Cardiovascular diseases (CVDs) a major contributor to global mortality rates, with a steadily rising prevalence observed across the world. Understanding the molecular mechanisms that underlie the signaling pathways implicated in the pathogenesis of CVDs represents a salient and advantageous avenue toward the development of precision and targeted therapeutics. A recent development in CVDs research is the discovery of long non-coding RNAs (lncRNAs), which are now understood to have crucial roles in the onset and development of several pathophysiological processes. The distinct expression patterns exhibited by lncRNAs in various CVDs contexts, present a significant opportunity for their utilization as both biomarkers and targets for therapeutic intervention. Among the various identified lncRNAs, HOX antisense intergenic RNA (HOTAIR) functions as signaling molecules that are significantly implicated in the pathogenesis of cardiovascular disorders in response to risk factors. HOTAIR has been observed to circulate within the bloodstream and possesses an integral epigenetic regulatory function in the transcriptional pathways of many diseases. Recent studies have suggested that HOTAIR offers promise as a biomarker for the detection and treatment of CVDs. The investigation on HOTAIR’s role in CVDs, however, is still in its early phases. The goal of the current study is to give a thorough overview of recent developments in the field of analyzing the molecular mechanism of HOTAIR in controlling the pathophysiological processes of CVDs as well as its possible therapeutic uses.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255007","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}
引用次数: 0
Cancer pharmacoinformatics: Databases and analytical tools 癌症药物信息学:数据库和分析工具
IF 3.9 4区 生物学
Functional & Integrative Genomics Pub Date : 2024-09-19 DOI: 10.1007/s10142-024-01445-5
Pradnya Kamble, Prinsa R. Nagar, Kaushikkumar A. Bhakhar, Prabha Garg, M. Elizabeth Sobhia, Srivatsava Naidu, Prasad V. Bharatam
{"title":"Cancer pharmacoinformatics: Databases and analytical tools","authors":"Pradnya Kamble,&nbsp;Prinsa R. Nagar,&nbsp;Kaushikkumar A. Bhakhar,&nbsp;Prabha Garg,&nbsp;M. Elizabeth Sobhia,&nbsp;Srivatsava Naidu,&nbsp;Prasad V. Bharatam","doi":"10.1007/s10142-024-01445-5","DOIUrl":"10.1007/s10142-024-01445-5","url":null,"abstract":"<div><p>Cancer is a subject of extensive investigation, and the utilization of omics technology has resulted in the generation of substantial volumes of big data in cancer research. Numerous databases are being developed to manage and organize this data effectively. These databases encompass various domains such as genomics, transcriptomics, proteomics, metabolomics, immunology, and drug discovery. The application of computational tools into various core components of pharmaceutical sciences constitutes \"Pharmacoinformatics\", an emerging paradigm in rational drug discovery. The three major features of pharmacoinformatics include (i) Structure modelling of putative drugs and targets, (ii) Compilation of databases and analysis using statistical approaches, and (iii) Employing artificial intelligence/machine learning algorithms for the discovery of novel therapeutic molecules. The development, updating, and analysis of databases using statistical approaches play a pivotal role in pharmacoinformatics. Multiple software tools are associated with oncoinformatics research. This review catalogs the databases and computational tools related to cancer drug discovery and highlights their potential implications in the pharmacoinformatics of cancer.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254969","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}
引用次数: 0
Deciphering the role of FOXP4 in long COVID: exploring genetic associations, evolutionary conservation, and drug identification through bioinformatics analysis 解密 FOXP4 在长 COVID 中的作用:通过生物信息学分析探索遗传关联、进化保护和药物鉴定
IF 3.9 4区 生物学
Functional & Integrative Genomics Pub Date : 2024-09-19 DOI: 10.1007/s10142-024-01451-7
Manoj Kumar Gupta, Gayatri Gouda, Ramakrishna Vadde
{"title":"Deciphering the role of FOXP4 in long COVID: exploring genetic associations, evolutionary conservation, and drug identification through bioinformatics analysis","authors":"Manoj Kumar Gupta,&nbsp;Gayatri Gouda,&nbsp;Ramakrishna Vadde","doi":"10.1007/s10142-024-01451-7","DOIUrl":"10.1007/s10142-024-01451-7","url":null,"abstract":"<div><p>Long COVID (LC) refers to a condition characterized by a variety of lingering symptoms that persist for more than 4 to 12 weeks following the initial acute SARS-CoV-2 infection. Recent research has suggested that the <i>FOXP4</i> gene could potentially be a significant factor contributing to LC. Owing to that, this study investigates <i>FOXP4</i>’s role in LC by analyzing public datasets to understand its evolution and expression in diverse human populations and searching for drugs to reduce LC symptoms. Population genetic analysis of <i>FOXP4</i> across human populations unmasks distinct genetic diversity patterns and positive selection signatures, suggesting potential population-specific susceptibilities to conditions like LC. Further, we also observed that <i>FOXP4</i> experiences high expression during LC. To identify potential inhibitors, drug screening analysis identifies synthetic drugs like Glisoxepide, and natural compounds Kapurimycin A3 produced from <i>Streptomyces sp</i>, and Cucurbitacin B from <i>Begonia nantoensis</i> as promising candidates. Overall, our research contributes to understanding how<i> FOXP4</i> may serve as a therapeutic target for mitigating the impact of LC.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254998","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}
引用次数: 0
C-FOS inhibition promotes pancreatic cancer cell ferroptosis by transcriptionally regulating the expression of SLC7A11 抑制 C-FOS 可通过转录调节 SLC7A11 的表达促进胰腺癌细胞的铁变态反应
IF 3.9 4区 生物学
Functional & Integrative Genomics Pub Date : 2024-09-18 DOI: 10.1007/s10142-024-01429-5
Shuangjia Wang, Hao Yu, Ping Guo, Liuxing Feng, Zhimin Li
{"title":"C-FOS inhibition promotes pancreatic cancer cell ferroptosis by transcriptionally regulating the expression of SLC7A11","authors":"Shuangjia Wang,&nbsp;Hao Yu,&nbsp;Ping Guo,&nbsp;Liuxing Feng,&nbsp;Zhimin Li","doi":"10.1007/s10142-024-01429-5","DOIUrl":"10.1007/s10142-024-01429-5","url":null,"abstract":"<div><p>Cellular proto-oncogene C-Fos forms the AP-1 transcription factor by dimerizing with proto-oncogene c-Jun; this factor upregulates the transcription of genes associated with different malignancies. However, its functions in pancreatic adenocarcinoma (PAAD) remain poorly understood. In this study, the c-Fos was increased in PAAD cells and tissues through bioinformatic analysis, RT-PCR, and WB. In two PAAD cell lines, PANC-1 and BxPC-3, we performed c-Fos knockdown studies using short hairpin RNA (shRNA). Functional analysis indicated that c-Fos depletion in PAAD cells inhibits cell proliferation and promotes ferroptosis. Chromatin Immunoprecipitation (ChIP) and Dual-luciferase experiments showed that c-Fos coupled to the promoter region of SLC7A11 stimulated its transcription, providing mechanistic insight into the process. Moreover, SLC7A11 blocked the decline of proliferation and ferroptosis by c-Fos knockdown in PAAD cells. Furthermore, a xenograft nude mouse model was established to study the impact of c-Fos on tumorigenesis in vivo. Depletion of c-Fos could suppress PC tumor growth and the expressions of SLC7A11, ki-67, and 4HNE, but overexpression of SLC7A11 reversed this process. In summary, our investigation has shown that c-Fos acts as a transcriptional regulator of SLC7A11, which may enhance tumour growth in pancreatic cancer by inhibiting ferroptosis. These results indicate that c-Fos might be a promising target for treating ferroptosis in PAAD.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255000","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}
引用次数: 0
Is the voltage-gated sodium channel β3 subunit (SCN3B) a biomarker for glioma? 电压门控钠通道β3亚基(SCN3B)是胶质瘤的生物标志物吗?
IF 3.9 4区 生物学
Functional & Integrative Genomics Pub Date : 2024-09-18 DOI: 10.1007/s10142-024-01443-7
Hengrui Liu, Jieling Weng, Christopher L.-H. Huang, Antony P. Jackson
{"title":"Is the voltage-gated sodium channel β3 subunit (SCN3B) a biomarker for glioma?","authors":"Hengrui Liu,&nbsp;Jieling Weng,&nbsp;Christopher L.-H. Huang,&nbsp;Antony P. Jackson","doi":"10.1007/s10142-024-01443-7","DOIUrl":"10.1007/s10142-024-01443-7","url":null,"abstract":"<div><p>Recent studies suggest a need for reliable biomarkers enhancing prognosis prediction and treatment strategies in cancer. Here, we performed a data analysis bearing on the expression of SCN3B, voltage-gated sodium channel (VGSC) β3 subunit, as a possible candidate for the development of a glioma biomarker for the first time. This extends our previous review article that mentioned the potential of SCN3B as a prognostic biomarker for glioma survival, further examining its association with existing indicators and immune responses. We utilized clinical and genomic data from multiple glioma cohorts. These include the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). We employed analytical techniques including time-dependent receiver operating characteristic (ROC) analysis, decision curves analysis (DCA), and correlation studies with immune checkpoint markers. Our findings indicate a differential SCN3B expression between glioma grades, and that this significantly correlates with patient survival, particularly in oligodendroglioma subtypes. The DCA curves suggested that the inclusion of SCN3B in the prognostic model would improve decision-making in these subtypes. Moreover, SCN3B expression positively correlated with the presence of key immune cells and negatively correlated with several immune checkpoint inhibitors. This suggests potential roles in modulating immune responses in glioma. Thus, SCN3B emerges as a promising potential prognostic biomarker for glioma, especially for oligodendroglioma. Its dual correlations with prognosis and immune regulation present a compelling case for further experimental and clinical investigations to establish its utility in enhancing glioma management strategies. These findings underscore the importance of integrating novel biomarkers with traditional prognostic models to refine treatment paradigms and improve patient outcomes.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254999","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}
引用次数: 0
Advances in targeting cancer epigenetics using CRISPR-dCas9 technology: A comprehensive review and future prospects 利用 CRISPR-dCas9 技术靶向癌症表观遗传学的进展:全面回顾与未来展望
IF 3.9 4区 生物学
Functional & Integrative Genomics Pub Date : 2024-09-18 DOI: 10.1007/s10142-024-01455-3
Jeevitha Rajanathadurai, Elumalai Perumal, Jospin Sindya
{"title":"Advances in targeting cancer epigenetics using CRISPR-dCas9 technology: A comprehensive review and future prospects","authors":"Jeevitha Rajanathadurai,&nbsp;Elumalai Perumal,&nbsp;Jospin Sindya","doi":"10.1007/s10142-024-01455-3","DOIUrl":"10.1007/s10142-024-01455-3","url":null,"abstract":"<div><p>Cancer, a complex and multifaceted group of diseases, continues to challenge the boundaries of medical science and healthcare. Its relentless impact on global health, both in terms of prevalence and mortality, underscores the urgent need for a comprehensive understanding of its underlying mechanisms and innovative therapeutic approaches. In recent years, significant progress has been achieved in identifying the genetic and epigenetic mechanisms that cause cancer development and treatment resistance. Researchers are currently investigating the possibility of epigenetic editing such as CRISPR-dCas9 (Clustered Regularly Interspaced Short Palindromic Repeats/deactivated CRISPR-associated protein 9) technologies, for targeting and modifying cancer related epigenetic alterations. A revolutionary form of precision cancer treatment called CRISPR-dCas9 is derived from the bacterial CRISPR-Cas (CRISPR-associated nuclease) system. CRISPR-dCas9 can be combined with epigenetic effectors (EE) to alter malignant epigenetic characteristics associated with cancer. The purpose of this review article is to provide a thorough analysis of recent advancements in utilizing CRISPR-dCas9 technology to target and modify epigenetic changes associated with cancer. This review aims to summarize the latest research developments, evaluate the effectiveness and limitations of CRISPR-dCas9 applications in cancer therapy, identify key challenges such as delivery methods and explore future directions for improving and expanding these technologies. Here, we address the various obstacles that may arise in clinical applications while showcasing the latest advancements and potential future uses of CRISPR-Cas9 in cancer therapy.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255002","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}
引用次数: 0
Tet1-mediated activation of the Ampk signaling by Trpv1 DNA hydroxymethylation exerts neuroprotective effects in a rat model of Parkinson’s disease 在帕金森病大鼠模型中,Tet1 通过 Trpv1 DNA 羟甲基化介导的 Ampk 信号激活具有神经保护作用
IF 3.9 4区 生物学
Functional & Integrative Genomics Pub Date : 2024-09-17 DOI: 10.1007/s10142-024-01446-4
Yu Fan, Po Wang, Changchun Jiang, Jinyu Chen, Meili Zhao, Jiahui Liu
{"title":"Tet1-mediated activation of the Ampk signaling by Trpv1 DNA hydroxymethylation exerts neuroprotective effects in a rat model of Parkinson’s disease","authors":"Yu Fan,&nbsp;Po Wang,&nbsp;Changchun Jiang,&nbsp;Jinyu Chen,&nbsp;Meili Zhao,&nbsp;Jiahui Liu","doi":"10.1007/s10142-024-01446-4","DOIUrl":"10.1007/s10142-024-01446-4","url":null,"abstract":"<div><p>Epigenetic regulation plays a role in Parkinson’s disease (PD), and ten-eleven translocation methylcytosine dioxygenase 1 (TET1) catalyzes the first step in DNA demethylation by converting 5-methylcytosine to 5-hydroxymethylcytosine. We investigated whether TET1 binds to the promoter of the transient receptor potential cation channel subfamily V member 1 (TRPV1) and regulates its expression, thereby controlling oxidative stress in PD. TRPV1 was identified as an oxidative stress-associated gene in the GSE20186 dataset including substantia nigra from 14 patients with PD and 14 healthy controls and the Genecards database. Lentiviral vectors were used to manipulate Trpv1 expression in rats, followed by 6-hydroxydopamine hydrochloride (6-OHDA) injection for modeling. Behavioral tests, immunofluorescence, Nissl staining, western blot assays, DHE fluorescent probe, biochemical analysis, and ELISA were conducted to assess oxidative stress and neurotoxicity. Trpv1 expression was significantly reduced in the brain tissues of 6-OHDA-treated Parkinsonian rats. Trpv1 alleviated behavioral dysfunction, oxidative stress, and dopamine neuron loss in rats. TET1 mediated TRPV1 hydroxymethylation to promote its expression, and Trpv1 inhibition reversed the mitigating effect of Tet1 on oxidative stress and behavioral dysfunction in PD. TRPV1 activated the AMPK signaling by promoting AMPK phosphorylation to alleviate neurotoxicity and oxidative stress in SH-SY5Y cells. Tet1-mediated Trpv1 hydroxymethylation modification promotes the Ampk signaling activation, thereby eliciting neuroprotection in 6-OHDA-treated Parkinsonian rats. These findings provide experimental evidence that targeting the TET1/TRPV1 axis may be neuroprotective for PD by acting on the AMPK signaling.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255004","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}
引用次数: 0
LncRNA XIST/miR-455-3p/HOXC4 axis promotes breast cancer development by activating TGF-β/SMAD signaling pathway LncRNA XIST/miR-455-3p/HOXC4轴通过激活TGF-β/SMAD信号通路促进乳腺癌发展
IF 3.9 4区 生物学
Functional & Integrative Genomics Pub Date : 2024-09-12 DOI: 10.1007/s10142-024-01442-8
Shanshan Zhao, Chen Song, Fengxi Chen, Man Li
{"title":"LncRNA XIST/miR-455-3p/HOXC4 axis promotes breast cancer development by activating TGF-β/SMAD signaling pathway","authors":"Shanshan Zhao,&nbsp;Chen Song,&nbsp;Fengxi Chen,&nbsp;Man Li","doi":"10.1007/s10142-024-01442-8","DOIUrl":"10.1007/s10142-024-01442-8","url":null,"abstract":"<div><p>Breast cancer is the second primary cause of cancer death among women. Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is a central regulator for X chromosome inactivation, and its abnormal expression is a primary feature of breast cancer. So far, the mechanism of XIST in breast cancer has not been fully elucidated. We attempted to illustrate the mechanism of XIST in breast cancer. The expressions of XIST, microRNA-455-3p (miR-455-3p) in breast cancer were measured using quantitative real-time PCR. The expressions of homeobox C4 (HOXC4) were assessed with immunohistochemical and Western blot. Also, the functions of XIST in breast cancer were assessed by Cell Counting Kit-8 analysis, colony formation assay, flow cytometry, Western blot, Transwell, and cell scratch assays. Meanwhile, the mechanism of XIST in breast cancer was validated using database analysis and dual-luciferase reporter assay. Furthermore, the function of XIST in breast cancer in vivo was estimated by tumor xenograft model, immunohistochemical assay, and hematoxylin-eosin staining. XIST and HOXC4 expressions were increased, but miR-455-3p expressions were decreased in breast cancer tissues and cells. Knocking down XIST restrained breast cancer cell proliferation, invasion, migration, epithelial-mesenchymal transformation (EMT), and induced cell cycle arrest at G0/G1. Meanwhile, XIST interacted with miR-455-3p, while miR-455-3p interacted with HOXC4. XIST knockdown repressed breast cancer cell proliferation, invasion, and EMT, while miR-455-3p inhibitor or HOXC4 overexpression abolished those impacts. HOXC4 overexpression also blocked the impacts of miR-455-3p mimic on breast cancer cell malignant behavior. In vivo experimental data further indicated that XIST knockdown repressed breast cancer cell tumorigenic ability, and decreased HOXC4 and p-SMAD3 (TGF-β/SMAD-related protein) expressions.XIST/miR-455-3p/HOXC4 facilitated breast cancer development by activating the TGF-β/SMAD pathway.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div><div><p>XIST/miR-455-3p/HOXC4 axis promotes breast cancer development by activating TGF-β/SMAD signaling pathway</p></div></div></figure></div></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142204790","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}
引用次数: 0
Exploring the transcription start sites and other genomic features facilitates the accurate identification and annotation of small RNAs across multiple stress conditions in Mycobacterium tuberculosis 探索转录起始位点和其他基因组特征有助于准确识别和注释结核分枝杆菌在多种压力条件下的小 RNA
IF 3.9 4区 生物学
Functional & Integrative Genomics Pub Date : 2024-09-12 DOI: 10.1007/s10142-024-01437-5
Hong-Leong Cheah, Marimuthu Citartan, Li-Pin Lee, Siti Aminah Ahmed, Mohd Zaki Salleh, Lay Kek Teh, Thean-Hock Tang
{"title":"Exploring the transcription start sites and other genomic features facilitates the accurate identification and annotation of small RNAs across multiple stress conditions in Mycobacterium tuberculosis","authors":"Hong-Leong Cheah,&nbsp;Marimuthu Citartan,&nbsp;Li-Pin Lee,&nbsp;Siti Aminah Ahmed,&nbsp;Mohd Zaki Salleh,&nbsp;Lay Kek Teh,&nbsp;Thean-Hock Tang","doi":"10.1007/s10142-024-01437-5","DOIUrl":"10.1007/s10142-024-01437-5","url":null,"abstract":"<div><p><i>Mycobacterium tub</i><i>erculosis</i> (MTB) is a pathogen that is known for its ability to persist in harsh environments and cause chronic infections. Understanding the regulatory networks of MTB is crucial for developing effective treatments. Small regulatory RNAs (sRNAs) play important roles in gene expression regulation in all kingdoms of life, and their classification based solely on genomic location can be imprecise due to the computational-based prediction of protein-coding genes in bacteria, which often neglects segments of mRNA such as 5’UTRs, 3’UTRs, and intercistronic regions of operons. To address this issue, our study simultaneously discovered genomic features such as TSSs, UTRs, and operons together with sRNAs in the <i>M. tuberculosis</i> H37Rv strain (ATCC 27294) across multiple stress conditions. Our analysis identified 1,376 sRNA candidates and 8,173 TSSs in MTB, providing valuable insights into its complex regulatory landscape. TSS mapping enabled us to classify these sRNAs into more specific categories, including promoter-associated sRNAs, 5’UTR-derived sRNAs, 3’UTR-derived sRNAs, true intergenic sRNAs, and antisense sRNAs. Three of these sRNA candidates were experimentally validated using 3’-RACE-PCR: predictedRNA_0240, predictedRNA_0325, and predictedRNA_0578. Future characterization and validation are necessary to fully elucidate the functions and roles of these sRNAs in MTB. Our study is the first to simultaneously unravel TSSs and sRNAs in MTB and demonstrate that the identification of other genomic features, such as TSSs, UTRs, and operons, allows for more accurate and specific classification of sRNAs.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142204809","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}
引用次数: 0
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