Methylation of mitochondrial DNA displacement loop region regulates mitochondrial copy number in colorectal cancer.
Methylation of mitochondrial DNA displacement loop region regulates mitochondrial copy number in colorectal cancer.
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线粒体 DNA 置换环区域的甲基化调节结直肠癌中的线粒体拷贝数
DOI：
10.3892/mmr.2017.7264
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发表时间：
2017-10
影响因子：
3.4
通讯作者：
Feng S
中科院分区：
文献类型：
--
作者：
Tong H;Zhang L;Gao J;Wen S;Zhou H;Feng S
目前尚不清楚线粒体DNA （mtDNA）位移环（D-loop）区域的去甲基化是否直接影响mtDNA拷贝数，进而改变结直肠癌的细胞周期、细胞凋亡和细胞增殖。目前的研究使用5种结直肠癌细胞系进行细胞活力测定、细胞周期分析和mtDNA甲基化分析。本研究结果表明，DNA低甲基化剂5-AZA -2 ' -脱氧胞苷（5-AZA）可显著促进Lovo和Colo-205结直肠癌细胞株的增殖。在Colo-205细胞中，5-AZA处理后，G0/G1期细胞比例增加。此外，5-AZA可降低Colo-205细胞的凋亡率。与对照组相比，5-AZA处理后，Colo-205和Lovo细胞的mtDNA拷贝数显著增加。值得注意的是，与5-AZA处理后的相应位点相比，Colo-205和Lovo细胞分别在D-loop区域的第4和第6 /7 CpG位点具有相对较高的甲基化水平。然而，在HCT116、SW480、LS-174T和HT-29细胞中，5-AZA处理未引起增殖、细胞周期、凋亡和mtDNA拷贝数的显著变化。5-AZA处理后，HCT116、SW480、LS-174T和HT-29细胞D-loop区的第4和第6 /7 CpG位点未观察到去甲基化。综上所述，D-loop启动子CpG岛上特定位点的去甲基化可能导致结直肠癌mtDNA拷贝数的升高，引发生物学行为的改变，包括细胞增殖增加、细胞凋亡减少和G0/G1期细胞周期的相对停滞。
It is not established whether de-methylation of the displacement loop (D-loop) region if mitochondrial DNA (mtDNA) directly influences mtDNA copy number and further alters the cell cycle, apoptosis and cell proliferation in colorectal cancer. The current study employed cell viability assays, cell cycle analysis, and mtDNA methylation analysis using 5 colorectal cancer cell lines. The present results demonstrated that 5-aza-2′-deoxycytidine (5-AZA), a DNA hypomethylating agent, significantly increased proliferation of Lovo and Colo-205 colorectal cancer cell lines. In Colo-205 cells, the proportion of G0/G1 phase cells was increased following 5-AZA treatment. Additionally, the apoptosis rate in Colo-205 cells was decreased by 5-AZA treatment. Compared with their controls, a significantly higher mtDNA copy number was observed in Colo-205 and Lovo cells following 5-AZA treatment. Notably, the Colo-205 and Lovo cells had relatively higher methylation levels at the 4 and 6th/7th CpG sites of D-loop region, respectively, compared with the levels at the corresponding sites following 5-AZA treatment. However, in HCT116, SW480, LS-174T, and HT-29 cells, 5-AZA treatment did not induce a significant change in proliferation, cell cycle, apoptosis and mtDNA copy number. Demethylation at the 4 and 6th/7th CpG sites of the D-loop region of HCT116, SW480, LS-174T and HT-29 cells was not observed following 5-AZA treatment. In conclusion, de-methylation of specific sites on CpG islands of D-loop promoter may lead to the elevation of mtDNA copy number in colorectal cancer, triggering alterations in biological behaviors, including increased cell proliferation, reduced apoptosis and a relative cell cycle arrest in G0/G1 phase.
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影响因子：
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作者：
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通讯作者：
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