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Revealing miRNAs' Janus-Faced Nature: Transforming Cold Tumours into Immunotherapy Hotspots and Overcoming Chemoresistance.
Pub Date : 2025-01-29 DOI: 10.2174/0122115366340113241216043551
Shinjini Sen, Ranu Nayak, Banashree Bondhopadhyay, Sudeep Bose

MicroRNA (miRNA) modulation has emerged as a promising strategy in cancer immunotherapy, particularly in converting "cold" tumors with limited immune cell infiltration into "hot" tumors responsive to immunotherapy. miRNAs regulate immune cell recruitment and activation within the tumor microenvironment, influencing tumor behavior targeting specific miRNAs in cold tumors aims to enhance the immune response, potentially improving therapeutic efficacy. Despite ongoing research challenges, such as tumor complexity and treatment resistance, miRNA-based therapies offer personalized approaches with potential ethical considerations. Advances in miRNA profiling may enable early cancer detection and tailored treatments, underscoring its role in future oncology. This review sheds light on the role of miRNA in cold and hot tumor microenvironments, how they modulate depending on the tumor niche and the current research challenges in implementing miRNA-based therapies include the complexity of tumors and their heterogeneity, which makes it difficult to identify the most relevant miRNAs to target. Additionally, treatment resistance can develop over time, reducing the effectiveness of miRNA modulation. Despite these challenges, ongoing research and advancements in miRNA profiling hold promise for overcoming these obstacles and improving the outcomes of cancer immunotherapy. To overcome the challenges of identifying relevant miRNAs to target, researchers can employ high-throughput sequencing techniques to comprehensively profile miRNA expression in different tumor subtypes. They can also utilize bioinformatics tools and databases to analyze the vast amount of miRNA-related data and identify potential candidate miRNAs. Furthermore, collaborations between scientists and clinicians can help validate the functional significance of identified miRNAs and their potential as therapeutic targets.

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引用次数: 0
Extrahepatic and Circulating miR-122: Diagnostic Implications and Future Directions.
Pub Date : 2025-01-23 DOI: 10.2174/0122115366334187250116164121
Rachel Sarah Royfman, Joseph Riley McTague, Meghana Ranabothu, Bindu Menon

Research on microRNAs is constantly expanding and evolving due to their role in the regulation of gene expression. miR-122, a 22-nucleotide microRNA, was first discovered as a liver-specific miRNA. Subsequently, it was found to be present in a wide range of tissues, such as the breast, testes, ovaries, and heart. The research on miR-122 in the liver has been extensive over the past few decades, leading to several important discoveries. However, its role in extrahepatic tissues is largely incompletely understood. Therefore, in light of the established clinical relevance of miR-122 as a potential biomarker and/or drug target in the liver, available information on miR-122 is compiled as it pertains to health and disease. This review discusses novel information generated in recent years and the corresponding progress in our understanding of the physiology of extrahepatic miR-122.

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引用次数: 0
micro-RNA 451-a as a Circulating Biomarker for Neuroblastoma. 微rna 451-a作为神经母细胞瘤的循环生物标志物
Pub Date : 2025-01-10 DOI: 10.2174/0122115366361597250108075627
Aditya Kumar Gupta, Aijaz Ahmad, Disha Kakker, Jagdish Prasad Meena, Ravi Kumar Majhi, Ambreen Jan, Rachna Seth, Venkateshawran Iyer, Saumyaranjan Mallick

Introduction: Micro ribonucleic acids (miRNAs) are small non-coding RNAs that modulate the expression of various genes. They have an important role in cancer pathogenesis. Differential expression of multiple miRNAs have been used as potential diagnostic and prognostic markers.

Methods: Various cancers have lately been employed as therapeutic targets. This prospective study included untreated pediatric neuroblastoma (NB) patients. In the discovery phase, global miRNA profiling was done using next-generation sequencing (NGS) on biopsy tissue samples of NB patients. In this phase, the top expressing miRNA was identified and chosen for further validation as circulating miRNA in blood samples of a different set of NB patients by real-time polymerase chain reaction (PCR).

Results: Based on the read counts on the global miRNA profiling in the discovery phase, we found that the miRNA that consistently had high reads across the majority of the NB samples were miRNA 451-a, 19b-3p, 106b-5p, and 21-5p. Of these, we selected miRNA 451-a and 19-b for the validation phase of the study as they had consistent overexpression. In the validation phase, the expression of the circulating miRNA 451-a in the blood was found to be higher. The average value for the relative fold (RF) expression for miRNA 451-a was 1.52.

Conclusion: miRNA 451-a is overexpressed both in the cancer tissue and the blood of NB patients. It can serve as a potential diagnostic marker. Further studies can elucidate its role in the pathogenesis of NB and it can have utility as a therapeutic target.

微核糖核酸(miRNAs)是一种小的非编码rna,可调节多种基因的表达。它们在癌症发病中起着重要作用。多种mirna的差异表达已被用作潜在的诊断和预后标志物。方法:近年来,各种癌症被用作治疗靶点。这项前瞻性研究纳入了未经治疗的小儿神经母细胞瘤(NB)患者。在发现阶段,使用新一代测序(NGS)对NB患者的活检组织样本进行了全球miRNA分析。在这一阶段,通过实时聚合酶链反应(real-time polymerase chain reaction, PCR),鉴定并选择表达最高的miRNA作为不同NB患者血液样本中的循环miRNA进行进一步验证。结果:基于发现阶段全球miRNA谱的读取计数,我们发现在大多数NB样本中始终具有高读取的miRNA是miRNA 451-a, 19b-3p, 106b-5p和21-5p。其中,我们选择了miRNA 451-a和19-b作为研究的验证阶段,因为它们具有一致的过表达。在验证阶段,血液中循环miRNA 451-a的表达量较高。miRNA 451-a的相对折叠(RF)表达的平均值为1.52。结论:miRNA 451-a在NB患者的癌组织和血液中均存在过表达。它可以作为潜在的诊断标记。进一步的研究可以阐明其在NB发病机制中的作用,并可作为治疗靶点。
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引用次数: 0
Evaluation of Salivary and Serum micro RNA 146a, 200c and its Target Gene PTEN in Chronic Periodontitis Patients and their Response to Non-Surgical Periodontal Therapy. 慢性牙周炎患者唾液和血清微RNA 146a、200c及其靶基因PTEN的评价及其对非手术牙周治疗的反应
Pub Date : 2025-01-08 DOI: 10.2174/0122115366319964241020165218
Jammula Surya Prasanna, Kunnel Apoorva

Background: Periodontitis destroys the tooth's supporting structures and attachment apparatus. Local or systemic factors can cause it. Traditionally, diagnosis is based on clinical parameters that may not consistently reflect an accurate confirmation. Biochemical and genetic analyses can provide deeper insights. MicroRNAs (miRNAs) regulate the immune and inflam-matory response to microbial pathogens. Detecting and evaluating miRNAs can be an important diagnostic parameter. This study aimed to assess the expression of miRNA 146a,200c, and its target gene PTEN to non-surgical periodontal therapy in serum and saliva.

Materials and methods: This interventional comparative study was conducted on 120 patients of both genders, ages between 35 and 55. Non-surgical periodontal therapy (NSPT) scaling and root planing were performed on all subjects, and their saliva and serum samples were collected before and after 8 weeks of NSPT. Quantitative rt-PCR (reverse transcriptase Polymerase Chain Reaction) analysis was conducted on all samples. The statistical analysis was done using SPSS version 22, and comparisons were made using paired t-tests, independent t-tests, and Pearson's correlation coefficient. The statistical significance level was set at a 'P' value of less than 0.05.

Results: It has been observed that there was a significant difference of miRNA in both serum and saliva samples 146a,200c, and the PTEN gene expression, from the beginning to 8 weeks. Sig-nificant variation was not observed when comparing the levels between serum and saliva.

Conclusion: miRNA 146A, 200c, and PTEN genes are interrelated with periodontitis. We can consider them as future biomarkers of periodontal diseases.

背景:牙周炎破坏牙齿的支撑结构和附着物。局部或全身因素都可能引起。传统上,诊断是基于临床参数,可能不能始终如一地反映准确的确认。生化和基因分析可以提供更深入的见解。MicroRNAs (miRNAs)调节对微生物病原体的免疫和炎症反应。检测和评估mirna可作为重要的诊断参数。本研究旨在评估血清和唾液中miRNA 146a、200c及其靶基因PTEN在牙周非手术治疗中的表达。材料与方法:本研究对年龄在35 ~ 55岁的120例男女患者进行介入性比较研究。对所有受试者进行非手术牙周治疗(NSPT)刮治和牙根刨平,并在NSPT治疗前和8周后采集唾液和血清样本。对所有样品进行定量rt-PCR(逆转录酶聚合酶链反应)分析。采用SPSS 22进行统计分析,采用配对t检验、独立t检验和Pearson相关系数进行比较。P < 0.05为统计学显著水平。结果:我们观察到,从开始到8周,血清和唾液样本146a,200c中miRNA以及PTEN基因表达均有显著差异。当比较血清和唾液之间的水平时,没有观察到显著的变化。结论:miRNA 146A、200c、PTEN基因与牙周炎相关。我们可以考虑将它们作为未来牙周病的生物标志物。
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引用次数: 0
A Robust NSCLC Biomarker- Mir-7-5p: Its In-Silico Validation and Potential SPR-Based Probe for Detection. 一个强大的NSCLC生物标志物- Mir-7-5p:其在硅验证和潜在的基于spr的检测探针。
Pub Date : 2025-01-01 DOI: 10.2174/0122115366325862241031071038
Chandrajeet Dhara, Anindita Dhara, Saumyatika Gantayat

MicroRNA abundance as a particular biomarker for precisely identifying cancer metastases has emerged in recent years. The expression levels of miRNA are analyzed to get insights into cancer tissue detection and subtypes. Similar to other cancer types, the miRNA shows high levels of target mRNA dysregulation in association with non-small cell lung carcinoma (NSCLC). Among many promising cancer biomarkers for NSCLC, miR-7-5p has shown significant down-regulation in the NSCLC tissues and targets proto-oncogenes like PAK2 and NOVA2. The ex-pression levels of different proto-oncogenes targeting the miR-7-5p in NSCLC showed that the EGFR-mutated NSCLC has an experimental validation. The target validation of the miR-7-5p could be analyzed using SPR (Surface plasmon resonance) based sensors at a single nanoparticle level, such as Au nanocube, due to its high specificity and accountability. Despite being an accountable tool for cancer diagnosis, miRNA-based biomarkers sometimes cause poor diagnostic specificity and reproducibility due to their heterogenicity and immunogenicity in cancer detection. To overcome these shortcomings, the biomarkers need to be validated according to recent clinical studies.

近年来,MicroRNA丰度作为一种精确识别癌症转移的特殊生物标志物已经出现。通过分析miRNA的表达水平来了解癌症组织检测和亚型。与其他类型的癌症相似,miRNA在非小细胞肺癌(NSCLC)中表现出高水平的靶mRNA失调。在许多有前景的NSCLC癌症生物标志物中,miR-7-5p在NSCLC组织中显示出显著下调,并靶向PAK2和NOVA2等原癌基因。不同靶向miR-7-5p的原癌基因在NSCLC中的表达水平表明egfr突变的NSCLC具有实验验证。由于其高特异性和可问责性,miR-7-5p的靶标验证可以使用基于SPR(表面等离子体共振)的传感器在单个纳米颗粒水平(如金纳米立方)进行分析。尽管作为一种可靠的癌症诊断工具,基于mirna的生物标志物在癌症检测中的异质性和免疫原性有时会导致较差的诊断特异性和可重复性。为了克服这些缺点,生物标志物需要根据最近的临床研究进行验证。
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引用次数: 0
The Role of Noncoding RNAs in the Prognosis and Diagnosis of Colorectal Cancer: An Emerging Biomarker. 非编码 RNA 在结直肠癌的预后和诊断中的作用:一种新兴的生物标志物
Pub Date : 2024-11-26 DOI: 10.2174/0122115366340944241122100236
O Surekha Vani, Kavitha R Thangaraj, Varshaa Ravichandran, Solomon F D Paul

Colorectal cancer has become the leading cause of death worldwide, and it is the second most common cancer in women and the third most common cancer in men. Accumulating evidence suggests that genetic and epigenetic factors play a key role in the development of colorectal cancer. Cancer Stem Cells (CSC) play an important role in the suppression or development of cancer in various conditions. In recent years, non-coding RNAs (ncRNA) have been the focus, and the association of CSC and non-coding RNA has played a crucial role in the development of human cancers. These non-coding RNAs are known to be expressed in many cancers. Studies have suggested that ncRNAs are dysregulated in colorectal cancer cells, and different factors, like Wnt and Notch, are involved in this dysregulation. ncRNAs play a significant role in cancer initiation, migration, and resistance to therapies. Moreover, long noncoding RNAs are known to regulate tumor suppressor genes or oncogenes. Targeting different ncRNAs like miRNA, circular RNA, long noncoding RNAs, and small interfering RNA may provide efficient, targeted therapeutic strategies for colon cancer treatment. This review aims to briefly discuss the latest findings on the role of noncoding RNAs in the prognosis and diagnosis of colon cancer.

结直肠癌已成为全球第一大死因,是女性第二大常见癌症,男性第三大常见癌症。越来越多的证据表明,遗传和表观遗传因素在结直肠癌的发展中起着关键作用。癌症干细胞(CSC)在各种情况下抑制或发展癌症方面发挥着重要作用。近年来,非编码 RNA(ncRNA)一直是关注的焦点,CSC 与非编码 RNA 的关联在人类癌症的发展中起着至关重要的作用。众所周知,这些非编码 RNA 在许多癌症中都有表达。研究表明,ncRNA 在结直肠癌细胞中表达失调,而 Wnt 和 Notch 等不同因子参与了这种失调。此外,众所周知,长非编码 RNA 可调控肿瘤抑制基因或致癌基因。针对不同的 ncRNA,如 miRNA、环状 RNA、长非编码 RNA 和小干扰 RNA,可为结肠癌治疗提供高效的靶向治疗策略。本综述旨在简要讨论非编码 RNA 在结肠癌预后和诊断中的作用的最新发现。
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引用次数: 0
Nanoparticle Carriers: A New Era of Precise CRISPR/Cas9 Gene Editing. 纳米粒子载体:精确 CRISPR/Cas9 基因编辑的新时代。
Pub Date : 2024-10-31 DOI: 10.2174/0122115366319848241022092805
Bhawna Sharma, Iti Chauhan, Gaurav Kumar, Khushboo Bhardwaj, Raj Kumar Tiwari

The revolutionary CRISPR/Cas9 gene editing technology holds immense potential for treating genetic diseases and tackling conditions like cancer. However, efficient delivery remains a significant challenge. This is where nanoparticles come into play, emerging as powerful allies in the realm of drug delivery. Nanoparticles can accommodate larger insertion sizes, enabling the incorporation of larger Cas9 enzymes and complex guide RNAs, thus opening up the possibility of editing previously inaccessible genetic regions. Their relatively straightforward and scalable production processes make them cost-effective options for wider applications. Notably, nanoparticles excel in vivo, demonstrating efficient tissue penetration and targeted delivery, which are crucial for maximizing therapeutic impact while minimizing side effects. This review aims to explore the potential of nanoparticle-based delivery systems for CRISPR/Cas9, highlighting their advantages and challenges in gene editing applications. The diverse range of nanoparticles further bolsters their potential. Polymeric nanoparticles, for instance, offer tunable properties for customization and controlled release of the CRISPR cargo. Lipid-based nanoparticles facilitate efficient cellular uptake and endosomal escape, ensuring the CRISPR components reach the target DNA. Even gold nanoparticles, known for their unique biocompatibility and photothermal properties, hold promise in light-activated editing strategies. Non-viral delivery systems, particularly those based on nanoparticles, stand out due to their inherent advantages. Collectively, the evidence paints a promising picture: nanoparticles are not merely passive carriers but active participants in the CRISPR/Cas9 delivery landscape. Their versatility, efficiency, and safety position them as key enablers of a future where gene editing can revolutionize drug development, offering personalized and targeted therapies for a wide range of diseases.

革命性的 CRISPR/Cas9 基因编辑技术在治疗遗传疾病和应对癌症等疾病方面具有巨大潜力。然而,高效给药仍然是一项重大挑战。这就是纳米颗粒发挥作用的地方,它是药物递送领域的强大盟友。纳米颗粒可以容纳更大的插入尺寸,从而能够加入更大的 Cas9 酶和复杂的引导 RNA,为编辑以前无法访问的基因区域提供了可能。它们的生产工艺相对简单且可扩展,使其在更广泛的应用中具有成本效益。值得注意的是,纳米颗粒在体内表现出色,具有高效的组织穿透性和靶向递送能力,这对于最大限度地提高治疗效果并减少副作用至关重要。本综述旨在探讨基于纳米颗粒的 CRISPR/Cas9 给药系统的潜力,突出它们在基因编辑应用中的优势和挑战。纳米颗粒的多样性进一步增强了它们的潜力。例如,聚合物纳米颗粒具有可调特性,可实现 CRISPR 货物的定制和可控释放。基于脂质的纳米颗粒可促进细胞的有效吸收和内泌体逃逸,确保 CRISPR 成分到达目标 DNA。即使是以其独特的生物相容性和光热特性而闻名的金纳米粒子,也有望用于光激活编辑策略。非病毒递送系统,尤其是基于纳米颗粒的系统,因其固有的优势而脱颖而出。总之,这些证据描绘了一幅充满希望的图景:纳米颗粒不仅仅是被动的载体,而是 CRISPR/Cas9 传输领域的积极参与者。它们的多功能性、高效性和安全性使其成为未来基因编辑彻底改变药物开发的关键推动力,为各种疾病提供个性化的靶向疗法。
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引用次数: 0
Identification of Key miRNAs in Endometriosis. 鉴定子宫内膜异位症的关键 miRNA。
Pub Date : 2024-10-25 DOI: 10.2174/0122115366333556241014115206
Francesca Blandino, Saviana Antonella Barbati, Luca Forlani, Giulia Coppola, Noemi Meschino, Ilde Cecchinelli, Antonietta Cosco Mazzuca, Valentina Veltri, Riccardo Giannico, Graziella Calugi

Introduction: Endometriosis, a prevalent gynecological disorder characterized by the presence of endometrial-like tissue outside the uterus, poses significant challenges in diagnosis and management due to its unclear pathogenesis and lack of specific biomarkers.

Objective: This study investigates the potential use of microRNAs (miRNAs) as key markers in endometriosis by studying two cohorts of patients (14 patients diagnosed with endometriosis and 15 patients with gynecological benign lesions, different from endometriosis).

Methods: MicroRNA sequencing analysis was tested within data management by a custom pipeline designed by Eurofins Genoma Group.

Results: We identified a specific miRNA expression profile associated with endometriosis to feature specific disease molecular clusters to further elucidate the underlying mechanisms driving endometriosis pathogenesis. Data from the present study suggest a specific miRNA scar for endometriosis compared to other gynecological diseases to develop screening tools in early diagnosis and to ameliorate the management of the disease itself.

Conclusion: This study lays the foundation for the identification of key miRNAs involved in the disease pathogenesis to unveil the molecular signatures in the complex scenario of endometriosis. Further validation and exploration of these findings are needed to develop tools to improve molecular diagnosis and to create a machine-learning prediction algorithm in the future.

导言:子宫内膜异位症是一种常见的妇科疾病,其特征是子宫腔外存在子宫内膜样组织,由于其发病机制不明确且缺乏特异性生物标志物,因此给诊断和治疗带来了巨大挑战:本研究通过对两组患者(14 名确诊为子宫内膜异位症的患者和 15 名患有妇科良性病变(不同于子宫内膜异位症)的患者)的研究,探讨了微RNA(miRNA)作为子宫内膜异位症关键标志物的潜在用途:方法:在Eurofins Genoma集团设计的定制流水线数据管理中测试了microRNA测序分析:结果:我们确定了与子宫内膜异位症相关的特定 miRNA 表达谱,以特定疾病分子群为特征,进一步阐明了子宫内膜异位症发病机制的内在驱动机制。本研究的数据表明,与其他妇科疾病相比,子宫内膜异位症有一个特定的 miRNA 瘢痕,可用于开发早期诊断的筛查工具,并改善疾病本身的治疗:本研究为鉴定参与疾病发病机制的关键 miRNAs 奠定了基础,从而揭示了子宫内膜异位症复杂情况下的分子特征。需要对这些发现进行进一步验证和探索,以开发改进分子诊断的工具,并在未来创建机器学习预测算法。
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引用次数: 0
Key LncRNAs Associated with Distant Metastasis in Breast Cancer: A System Biology Analysis. 与乳腺癌远处转移相关的关键 LncRNAs:系统生物学分析
Pub Date : 2024-10-25 DOI: 10.2174/0122115366319044241015065537
Shakila Mohammadi, Mina Dehghani-Samani, Khatereh Firouzi-Farsani, Mohsen Dibaj, Shahrzad Zhaeentan

Introduction: Breast cancer (BC) is the most prevalent cancer among women globally. Metastasis is the leading cause of mortality in most cancers. Early BC detection before metastasis can enhance survival rates. Understanding BC metastasis mechanisms could aid in developing metastasis-specific treatments.

Method: The role of long non-coding RNAs (lncRNA) in cancer progression is recognized, yet the importance of specific lncRNAs in BC, despite potential alterations, remains inadequately explored. We utilized bioinformatics tools to identify novel lncRNAs dysregulated in metastasis. To achieve this objective, the gene expression profile of GSE102484, encompassing metastatic and non-metastatic BC tissue samples, was analyzed using the limma package in R with cut-off criteria set at an adjusted p-value < 0.005 and |fold change (FC)| ≥ 0.5. We used WGCNA analysis to find co-expression genes for lncRNAs. Then, we identified hub genes and performed pathway enrichment to better understand the results. Considering the defined criteria, eight novels of dysregulated lncRNAs and top 10 miRNAs were identified.

Result: Dysregulated lncRNAs are found in yellow, green, brown, purple, and turquoise co-expression modules from WGCNA analysis. Enrichment analysis of these co-expressed modules revealed relevant pathways to metastasis, such as epithelial-to-mesenchymal transition and integrin cell-surface interactions, as well as regulation of HIF1-alpha. In addition, SDPR, TGFB1I1, ILF3, KIF4A, and COL5A1 were identified as hub genes. Based on DElncRNA-miRNADEmRNA connections and co-expression, we ultimately constructed lncRNA-associated ceRNA axes.

Conclusion: The current study may identify novel lncRNAs implicated in BC metastasis; still, additional research is required to determine the potential functions of these lncRNAs in BC metastasis.

导言乳腺癌(BC)是全球妇女中发病率最高的癌症。转移是大多数癌症的主要致死原因。在乳腺癌转移之前及早发现可提高生存率。了解 BC 转移机制有助于开发针对转移的治疗方法:方法:长非编码RNA(lncRNA)在癌症进展中的作用已得到公认,但特定lncRNA在BC中的重要性(尽管存在潜在的改变)仍未得到充分探索。我们利用生物信息学工具来鉴定转移中调控失调的新型 lncRNA。为了实现这一目标,我们使用 R 中的 limma 软件包分析了 GSE102484(包括转移性和非转移性 BC 组织样本)的基因表达谱,截断标准设定为调整后 p 值小于 0.005 且 |fold change (FC)| ≥ 0.5。我们使用 WGCNA 分析查找 lncRNA 的共表达基因。然后,我们确定了枢纽基因,并进行了通路富集以更好地理解结果。根据所定义的标准,我们确定了8种失调的lncRNA和前10种miRNA:结果:通过WGCNA分析,在黄色、绿色、棕色、紫色和绿松石色的共表达模块中发现了失调的lncRNA。这些共表达模块的富集分析揭示了转移的相关途径,如上皮细胞向间质转化、整合素细胞表面相互作用以及HIF1-α的调控。此外,SDPR、TGFB1I1、ILF3、KIF4A 和 COL5A1 也被确定为枢纽基因。基于DElncRNA-miRNADEmRNA的连接和共表达,我们最终构建了与lncRNA相关的ceRNA轴:目前的研究可能发现了与BC转移有关的新型lncRNAs;但要确定这些lncRNAs在BC转移中的潜在功能,还需要进行更多的研究。
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引用次数: 0
Identification of miR-20a as a Diagnostic and Prognostic Biomarker in Colorectal Cancer: MicroRNA Sequencing and Machine Learning Analysis. 鉴定 miR-20a 作为结直肠癌诊断和预后生物标记物:MicroRNA 测序和机器学习分析。
Pub Date : 2024-09-24 DOI: 10.2174/0122115366320538240912080053
Hamid Jamialahmadi, Alireza Asadnia, Ghazaleh Khalili-Tanha, Reza Mohit, Hanieh Azari, Majid Khazaei, Mina Maftooh, Mohammadreza Nassiri, Seyed Mahdi Hassanian, Majid Ghayour-Mobarhan, Gordon A Ferns, Elham Nazari, Amir Avan

Introduction: The differential expression of miRNAs, a key regulator in many cell signaling pathways, has been studied in various malignancies and may have an important role in cancer progression, including colorectal cancer (CRC).

Method: The present study used machine learning and gene interaction study tools to explore the prognostic and diagnostic value of miRNAs in CRC. Integrative analysis of 353 CRC samples and normal tissue data was obtained from the TCGA database and further analyzed by R packages to define the deferentially expressed miRNAs (DEMs). Furthermore, machine learning and Kaplan Meier survival analysis helped better specify the significant prognostic value of miRNAs. A combination of online databases was then used to evaluate the interactions between target genes, their molecular pathways, and the correlation between the DEMs.

Result: The results indicated that miR-19b and miR-20a have a significant prognostic role and are associated with CRC progression. The ROC curve analysis discovered that miR-20a alone and combined with other miRNAs, including hsa-mir-21 and hsa-mir-542, are diagnostic biomarkers in CRC. In addition, 12 genes, including NTRK2, CDC42, EGFR, AGO2, PRKCA, HSP90AA1, TLR4, IGF1, ESR1, SMAD2, SMAD4, and NEDD4L, were found to be the highest score targets for these miRNAs. Pathway analysis identified the two correlated tyrosine kinase and MAPK signaling pathways with the key interaction genes, i.e., EGFR, CDC42, and HSP90AA1.

Conclusion: To better define the role of these miRNAs, the ceRNA network, including lncRNAs, was also prepared. In conclusion, the combination of R data analysis and machine learning provides a robust approach to resolving complicated interactions between miRNAs and their targets.

导言:miRNA是许多细胞信号通路的关键调控因子,在各种恶性肿瘤中的差异表达已被研究,并可能在包括结直肠癌(CRC)在内的癌症进展中发挥重要作用:本研究利用机器学习和基因相互作用研究工具来探讨 miRNAs 在 CRC 中的预后和诊断价值。研究人员从 TCGA 数据库中获取了 353 个 CRC 样本和正常组织的整合分析数据,并使用 R 软件包对这些数据进行了进一步分析,从而确定了递延表达的 miRNAs(DEMs)。此外,机器学习和卡普兰-梅耶尔生存分析有助于更好地明确 miRNA 的重要预后价值。然后,结合在线数据库评估了靶基因之间的相互作用、其分子通路以及 DEMs 之间的相关性:结果:研究结果表明,miR-19b和miR-20a具有重要的预后作用,与CRC的进展相关。ROC曲线分析发现,miR-20a单独或与其他miRNA(包括hsa-mir-21和hsa-mir-542)结合,都是CRC的诊断生物标志物。此外,研究还发现 NTRK2、CDC42、表皮生长因子受体、AGO2、PRKCA、HSP90AA1、TLR4、IGF1、ESR1、SMAD2、SMAD4 和 NEDD4L 等 12 个基因是这些 miRNA 的最高得分靶标。通路分析确定了与关键相互作用基因(即表皮生长因子受体、CDC42 和 HSP90AA1)相关的两个酪氨酸激酶和 MAPK 信号通路:为了更好地界定这些 miRNAs 的作用,还编制了包括 lncRNAs 在内的 ceRNA 网络。总之,R数据分析与机器学习的结合为解决miRNA与其靶标之间复杂的相互作用提供了一种稳健的方法。
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引用次数: 0
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MicroRNA (Shariqah, United Arab Emirates)
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