Correlation between increased ND2 expression and demethylated displacement loop of mtDNA in colorectal cancer
Correlation between increased ND2 expression and demethylated displacement loop of mtDNA in colorectal cancer
复制标题
DOI：
10.3892/mmr.2012.870
复制
发表时间：
2012-07-01
影响因子：
3.4
通讯作者：
Yang, Huijun
中科院分区：
文献类型：
--
作者：
Feng, Shi;Xiong, Lili;Yang, Huijun
细胞糖代谢的改变被认为是癌细胞的生化标志。线粒体是葡萄糖代谢发生的关键细胞器。然而，线粒体DNA （mtDNA）位移环（D-loop）区域的DNA甲基化是否影响限速酶的表达，从而影响结直肠癌的氧化磷酸化，仍有待确定。在结直肠癌的发生和发展过程中，ND2 （NADH的一个亚基）的定量变化和d -环的甲基化状态被观察到。此外，还研究了其与临床病理分期的可能相关性。在2008年至2009年间，对44例结直肠癌患者的肿瘤和相应的非癌组织进行手术切除。所有标本定量Cox IV表达，计算ND2表达量。ND2表达量的变化明显增加。肿瘤组织中ND2含量的平均相对比值为1.67 +/- 0.44，相应非癌组织中ND2含量的平均相对比值为0.89 +/- 0.44 （p < 0.01）。此外，大多数相应的非癌组织的D-loop甲基化比例为79.5%，而肿瘤组织的这一比例要小得多（11.4%）。在与临床病理资料相关后，ND2在结直肠癌中的表达变化与临床病理分期有显著相关性。此外，在肿瘤和相应的非癌组织中，未甲基化的D-loop病例的比例都增加了，ND2的表达也从I期到IV期增加。我们的研究结果表明，在结直肠癌的发生和/或进展过程中，D-loop的去甲基化在调节ND2的表达中起着关键作用。
Change in cellular glucose metabolism is considered to be a biochemical hallmark in cancer cells. The mitochondrion is the key organelle in which glucose metabolism occurs. However, whether DNA methylation at the displacement loop (D-loop) region of mitochondrial DNA (mtDNA) has an effect on the expression of the rate-limiting enzyme, and, therefore, on oxidative phosphorylation in colorectal cancer remains to be determined. Quantitative change in ND2 (a subunit of NADH) and the methylation status of the D-loop were observed during the initiation and progression of colorectal cancer. Furthermore, the possible correlations with clinicopathological stage were also investigated. Tumor and corresponding non-cancerous tissues were surgically resected from 44 colorectal cancer patients between 2008 and 2009. Cox IV expression was quantified in all of the specimens, and the ND2 expression was calculated. Quantitative changes in ND2 expression exhibited a significant increase. The average relative ratios of ND2 content were 1.67 +/- 0.44 in the tumor tissues and 0.89 +/- 0.44 in the corresponding non-cancerous tissues (p < 0.01). In addition, the D-loop of most corresponding non-cancerous tissues was methylated and the percentage was 79.5%, while this percentage was much smaller in the tumor tissues (11.4%). Following correlation with clinicopathological data, changes in the ND2 expression in the colorectal cancer exhibited a significant association with clinicopathological stage. This increase was significant as early as in stage I. Furthermore, the ratios of unmethylated D-loop cases were increased in both tumor and corresponding non-cancerous tissues, and the ND2 expression was also increased from stages I to IV. Our results indicate that demethylation of the D-loop plays a key role in regulating ND2 expression during the initiation and/or progression of colorectal cancer.