Identification of MYEOV-Associated Gene Network as a Potential Therapeutic Target in Pancreatic Cancer.
Identification of MYEOV-Associated Gene Network as a Potential Therapeutic Target in Pancreatic Cancer.
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探索胰腺癌的关键分子调控机制对研究胰腺癌的治疗策略至关重要。为了精确识别关键的胰腺癌基因，我们使用了多种分析综合方法。我们对发现的关键基因MYEOV进行基因关联分析，构建了以MYEOV为核心的分子网络。这个分子网络中的基因可能通过肿瘤免疫细胞浸润共同影响胰腺癌的发展。这是首次报道MYEOV可能作为ceRNA与一些胰腺癌相关基因（如KRAS）形成相互作用网络，并作为胰腺癌治疗的战略治疗靶点。胰腺癌发生的分子机制尚不清楚，因此寻找胰腺癌相关重要基因的分子网络具有重要意义。为寻找胰腺癌的关键分子，分别采用Deseq2包、edgeR包和limma-voom包进行差异基因表达分析。采用COX生存分析分析胰腺癌生存相关基因。最后，我们综合了这些结果，得到了显著差异表达基因MYEOV（骨髓瘤过表达基因），它与胰腺癌的生存关系最为密切。qRT-PCR实验证实，MYEOV mRNA在胰腺癌细胞中的转录水平明显高于正常人胰导管上皮细胞（HPDE）。通过对多个数据库的综合分析，我们构建了一个以MYEOV为中心的分子网络，并发现了该网络中分子与肿瘤相关免疫细胞之间的特异性联系。我们注意到MYEOV可以作为一种ceRNA，通过对hsa-miR-103a-3p和hsa-miR-107产生分子海绵作用，从而影响GPRC5A、SERPINB5、EGFR、KRAS、EIF4G2和PDCD4在胰腺癌进展中的作用。此外，我们还发现浸润的免疫细胞是myeov相关网络中分子促进胰腺癌进展的潜在介质。这是首次报道MYEOV可能作为竞争性内源性RNA （ceRNA）与一些胰腺癌相关基因（如KRAS）形成相互作用网络，并作为胰腺癌治疗的关键靶点。
Exploring the key molecular regulatory mechanism of pancreatic cancer is crucial to investigate the therapeutic strategies for pancreatic cancer. To precisely identify key pancreatic cancer genes, we used a multiple analyses integrated approach. We performed gene association analysis on the key gene MYEOV we discovered, which led to a molecular network with MYEOV as the core. The genes in this molecular network could work together to influence the development of pancreatic cancer, possibly through protumor immune cell infiltration. It is the first report to focus on the possibility that MYEOV may act as a ceRNA to form an interaction network with some pancreatic cancer-related genes such as KRAS and serve as a strategic therapeutic target of pancreatic cancer treatment. The molecular mechanism that promotes pancreatic cancer remains unclear, so it is important to find the molecular network of important genes related to pancreatic cancer. To find the key molecule of pancreatic cancer, differential gene expression analyses were analyzed by the Deseq2 package, edgeR package, and limma-voom package, respectively. Pancreatic cancer survival-related genes were analyzed by COX survival analysis. Finally, we integrated the results to obtain the significantly differentially expressed gene, MYEOV (myeloma overexpressed gene), most strongly related to survival in pancreatic cancer. Experimental verification by qRT-PCR confirmed that transcription levels of MYEOV mRNA markedly increased in pancreatic cancer cells relative to normal human pancreatic ductal epithelial cells (HPDE). Through the comprehensive analysis of multiple databases, we constructed a molecular network centered on MYEOV and found specific links between molecules in this network and tumor-associated immune cells. It was noted that MYEOV could serve as a ceRNA by producing molecular sponging effects on hsa-miR-103a-3p and hsa-miR-107, thus affecting the role of GPRC5A, SERPINB5, EGFR, KRAS, EIF4G2, and PDCD4 on pancreatic cancer progression. Besides, we also identified that infiltrated immune cells are potential mediators for the molecules in the MYEOV-related network to promote pancreatic cancer progression. It is the first report to focus on the possibility that MYEOV may act as a competing endogenous RNA (ceRNA) to form an interactive network with some pancreatic cancer-related genes such as KRAS and serve as a key therapeutic target of pancreatic cancer treatment.
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影响因子：
4.4
作者：
Puente XS;Velasco G;Gutiérrez-Fernández A;Bertranpetit J;King MC;López-Otín C
通讯作者：
López-Otín C
影响因子：
11.1
作者：
Greenhough A;Bagley C;Heesom KJ;Gurevich DB;Gay D;Bond M;Collard TJ;Paraskeva C;Martin P;Sansom OJ;Malik K;Williams AC
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Williams AC
影响因子：
15.9
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通讯作者：
di Magliano, Marina Pasca
影响因子：
8
作者：
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影响因子：
10.1
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Lutz ER;Wu AA;Bigelow E;Sharma R;Mo G;Soares K;Solt S;Dorman A;Wamwea A;Yager A;Laheru D;Wolfgang CL;Wang J;Hruban RH;Anders RA;Jaffee EM;Zheng L
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