Burch Tanya C, Rhim Johng S, Nyalwidhe Julius O
Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, 651 Colley Avenue, Lester Hall Suite 424, Norfolk, VA 23507, USA; Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, 651 Colley Avenue, Lester Hall Suite 424, Norfolk, VA 23507, USA.
Department of Surgery, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
Biomed Res Int. 2016;2016:1785201. doi: 10.1155/2016/1785201. Epub 2016 Jul 10.
Background. The most significant hallmarks of cancer are directly or indirectly linked to deregulated mitochondria. In this study, we sought to profile mitochondria associated genes in isogenic prostate cell lines with different tumorigenic phenotypes from the same patient. Results. Two isogenic human prostate cell lines RC77N/E (nonmalignant cells) and RC77T/E (malignant cells) were profiled for expression of mitochondrial biogenesis and energy metabolism genes by qRT-PCR using the Human Mitochondria and the Mitochondrial Energy Metabolism RT(2) PCR arrays. Forty-seven genes were differentially regulated between the two cell lines. The interaction and regulatory networks of these genes were generated by Ingenuity Pathway Analysis. UCP2 was the most significantly upregulated gene in primary adenocarcinoma cells in the current study. The overexpression of UCP2 upon malignant transformation was further validated using human prostatectomy clinical specimens. Conclusions. This study demonstrates the overexpression of multiple genes that are involved in mitochondria biogenesis, bioenergetics, and modulation of apoptosis. These genes may play a role in malignant transformation and disease progression. The upregulation of some of these genes in clinical samples indicates that some of the differentially transcribed genes could be the potential targets for therapeutic interventions.
背景。癌症最显著的特征直接或间接与线粒体失调有关。在本研究中,我们试图分析来自同一患者具有不同致瘤表型的同基因前列腺细胞系中的线粒体相关基因。结果。使用人类线粒体和线粒体能量代谢RT(2) PCR阵列,通过qRT-PCR分析了两种同基因人类前列腺细胞系RC77N/E(非恶性细胞)和RC77T/E(恶性细胞)中线粒体生物发生和能量代谢基因的表达。两种细胞系之间有47个基因存在差异调节。这些基因的相互作用和调控网络通过 Ingenuity 通路分析生成。在本研究中,UCP2是原发性腺癌细胞中上调最显著的基因。使用人类前列腺切除临床标本进一步验证了恶性转化时UCP2的过表达。结论。本研究证明了多个参与线粒体生物发生、生物能量学和凋亡调节的基因过表达。这些基因可能在恶性转化和疾病进展中起作用。临床样本中其中一些基因的上调表明一些差异转录基因可能是治疗干预的潜在靶点。