Transcriptional profiling revealed the anti-proliferative effect of MFN2 deficiency and identified risk factors in lung adenocarcinoma
Transcriptional profiling revealed the anti-proliferative effect of MFN2 deficiency and identified risk factors in lung adenocarcinoma
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转录谱揭示了 MFN2 缺陷的抗增殖作用，并确定了肺腺癌的危险因素。
DOI：
10.1007/s13277-015-4702-6
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Han Baohui
中科院分区：
文献类型：
--
作者：
Lou Yuqing;Zhang Yanwei;Li Rong;Gu Ping;Xiong Liwen;Zhong Hua;Zhang Wei;Han Baohui
线粒体融合蛋白2（Mitofusin-2，MFN 2）最初被鉴定为高血压大鼠动脉中过度增殖的血管平滑肌细胞（VSMCs）的增生抑制剂，其也与多种癌症有关。它是否是一种癌基因，是否对肿瘤细胞具有抗增殖作用，目前还存在争议。我们之前的细胞周期分析和MTT法显示，在MFN 2缺陷的A549人肺腺癌细胞中，细胞增殖受到抑制，但没有研究调控网络的变化或解决潜在的机制。在这里，我们在MFN 2敲低的A549细胞中进行了表达谱分析，发现癌症相关通路是MFN 2缺陷最敏感的通路之一。通过与来自癌症基因组图谱（TCGA）的61对肿瘤-正常匹配样本组成的队列的表达谱进行比较，我们梳理出了MFN 2消融对A549细胞影响的具体途径，并确定了一些表达水平与临床病理参数相关的基因。此外，转录因子靶富集分析确定E2 F作为一个潜在的转录因子，是失调的MFN 2缺陷。虽然生物信息学分析通常需要进一步验证，但我们的研究为相关领域的未来科学探究提供了相当多的信息，并为表征调控网络中的扰动提供了范例。
Mitofusin-2 (MFN2) was initially identified as a hyperplasia suppressor in hyper-proliferative vascular smooth muscle cells (VSMCs) of hypertensive rat arteries, which has also been implicated in various cancers. There exists a controversy in whether it is an oncogene or exerting anti-proliferative effect on tumor cells. Our previous cell cycle analysis and MTT assay showed that cell proliferation was inhibited in MFN2 deficient A549 human lung adenocarcinoma cells, without investigating the changes in regulatory network or addressing the underlying mechanisms. Here, we performed expression profiling in MFN2 knockdown A549 cells and found that cancer-related pathways were among the most susceptible pathways to MFN2 deficiency. Through comparison with expression profiling of a cohort consisting of 61 pairs of tumor-normal matched samples from The Cancer Genome Atlas (TCGA), we teased out the specific pathways to address the impact that MFN2 ablation had on A549 cells, as well as identified a few genes whose expression level associated with clinicopathologic parameters. In addition, transcriptional factor target enrichment analysis identified E2F as a potential transcription factor that was deregulated in response to MFN2 deficiency. Although bioinformatics analysis usually entail further verification, our study provided considerable information for future scientific inquiries in related areas as well as a paradigm for characterizing perturbation in regulatory network.
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影响因子：
8.8
作者：
通讯作者：
--
DOI：
--
发表时间：
2008
期刊：
--
影响因子：
--
作者：
A. Thakur;Aliccia B. Bollig;Jiusheng Wu;D. Liao;Jiusheng;J. Liao
通讯作者：
A. Thakur;Aliccia B. Bollig;Jiusheng Wu;D. Liao;Jiusheng;J. Liao
影响因子：
2.8
作者：
Sharma, Jaya;Gray, Kathryn P.;Sweeney, Christopher J.
通讯作者：
Sweeney, Christopher J.
Mfn2 在胃癌中的抗肿瘤作用
影响因子：
5.6
作者：
Zhang GE;Jin HL;Lin XK;Chen C;Liu XS;Zhang Q;Yu JR
通讯作者：
Yu JR
影响因子：
11.2
作者：
A. Dallol;N. F. da Silva;P. Viacava;J. Minna;I. Bièche;E. Maher;F. Latif
通讯作者：
A. Dallol;N. F. da Silva;P. Viacava;J. Minna;I. Bièche;E. Maher;F. Latif