Shakila Mohammadi, Mina Dehghani-Samani, Khatereh Firouzi-Farsani, Mohsen Dibaj, Shahrzad Zhaeentan
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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.</p><p><strong>Result: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Key LncRNAs Associated with Distant Metastasis in Breast Cancer: A System Biology Analysis.\",\"authors\":\"Shakila Mohammadi, Mina Dehghani-Samani, Khatereh Firouzi-Farsani, Mohsen Dibaj, Shahrzad Zhaeentan\",\"doi\":\"10.2174/0122115366319044241015065537\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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.</p><p><strong>Method: </strong>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.</p><p><strong>Result: </strong>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. 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引用次数: 0
摘要
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。
Key LncRNAs Associated with Distant Metastasis in Breast Cancer: A System Biology Analysis.
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.