在结肠ρ（rho0）细胞中，线粒体功能降低介导了与癌症相关的转录组改变。
In colonic ρ (rho0) cells reduced mitochondrial function mediates transcriptomic alterations associated with cancer.
作者信息
Penrose Harrison M, Heller Sandra, Cable Chloe, Nakhoul Hani, Ungerleider Nate, Baddoo Melody, Pursell Zachary F, Flemington Erik K, Crawford Susan E, Savkovic Suzana D
机构信息
Department of Pathology and Laboratory Medicine, Tulane University, New Orleans, LA 70112, USA.
Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
出版信息
Oncoscience. 2017 Dec 27;4(11-12):189-198. doi: 10.18632/oncoscience.386. eCollection 2017 Nov.
BACKGROUND
Mitochondrial reprogramming has emerged as a hallmark of cancer pathobiology. Although it is believed this reprogramming is essential for cancer cells to thrive, how it supports cancer pathobiology is unclear. We previously generated colonic ρ0 (rho0) cells with reduced mitochondrial energy function and acquired their transcriptional signature. Here, we utilized a bioinformatics approach to identify their changes linked to cancer pathobiology.
METHODS
Human colon cancer HCT116 cells, control and ρ0, were used for qPCR. Bioinformatics analysis: GeneCards, Kaplan-Meier Survival, GENT, cBioPortal.
RESULTS
The colonic ρ0 transcriptome was linked with proliferation, DNA replication, survival, tumor morphology, and cancer. Among differentially expressed transcripts, 281 were regulators or biomarkers of human colon cancer especially those with inflammatory microsatellite instability (MSI). We identified and validated novel transcripts in ρ0 cells with altered expression in human colon cancer. Among them DGK1, HTR7, FLRT3, and ZBTB18 co-occurred with established regulators of human colon cancer pathobiology. Also, increased levels of DGKI, FLRT3, ZBTB18, and YPEL1 as well as decreased levels of HTR7, and CALML6 were linked to substantially poorer patient survival.
CONCLUSION
We identified established and novel regulators in colon cancer pathobiology that are dependent on mitochondrial energy reprogramming and linked to poorer patient survival.
背景
线粒体重编程已成为癌症病理生物学的一个标志。尽管人们认为这种重编程对癌细胞的存活至关重要，但它如何支持癌症病理生物学尚不清楚。我们之前生成了线粒体能量功能降低的结肠ρ0（rho0）细胞，并获得了它们的转录特征。在此，我们利用生物信息学方法来识别与癌症病理生物学相关的变化。
方法
使用人结肠癌HCT116细胞、对照细胞和ρ0细胞进行定量聚合酶链反应。生物信息学分析：基因卡片、卡普兰 - 迈耶生存分析、基因表达数据库（GENT）、cBioPortal。
结果
结肠ρ0转录组与增殖、DNA复制、存活、肿瘤形态和癌症相关。在差异表达的转录本中，281个是人类结肠癌的调节因子或生物标志物，尤其是那些具有炎症性微卫星不稳定性（MSI）的标志物。我们在ρ0细胞中鉴定并验证了在人类结肠癌中表达改变的新转录本。其中，二酰甘油激酶1（DGK1）、5 - 羟色胺受体7（HTR7）、成纤维细胞生长因子调节酪氨酸激酶3（FLRT3）和锌指蛋白18（ZBTB18）与人类结肠癌病理生物学的既定调节因子同时出现。此外，DGKI、FLRT3、ZBTB18和YPEL1水平升高以及HTR7和钙调蛋白L6（CALML6）水平降低与患者生存率显著降低相关。
结论
我们在结肠癌病理生物学中鉴定出了既定的和新的调节因子，它们依赖于线粒体能量重编程，并与较差的患者生存率相关。
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