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早期结直肠病变和肿瘤中 microRNA-137 和 microRNA-342 基因座的差异 DNA 高甲基化模式。

The Differential DNA Hypermethylation Patterns of microRNA-137 and microRNA-342 Locus in Early Colorectal Lesions and Tumours.

机构信息

Institue of Pathology, University of Bern, 3010 Bern, Switzerland.

Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 19839-63113, Iran.

出版信息

Biomolecules. 2019 Sep 21;9(10):519. doi: 10.3390/biom9100519.

DOI:10.3390/biom9100519
PMID:31546665
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6843302/
Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, representing 13% of all cancers. The role of epigenetics in cancer diagnosis and prognosis is well established. MicroRNAs in particular influence numerous cancer associated processes including apoptosis, proliferation, differentiation, cell-cycle controls, migration/invasion and metabolism. MiRNAs-137 and 342 are exon- and intron-embedded, respectively, acting as tumour-suppressive microRNA via hypermethylation events. Levels of miRNAs 137 and 342 have been investigated here as potential prognostic markers for colorectal cancer patients. The methylation status of miRNA-137 and miRNA-342 was evaluated using methylation-specific (MSP) polymerase chain reaction (PCR) on freshly frozen tissue derived from 51 polyps, 8 tumours and 14 normal colon mucosa specimens. Methylation status of miRNA-137 and miRNA-342 was significantly higher in tumour lesions compared to normal adjacent mucosa. Surprisingly, the methylation frequency of miR-342 (76.3%) among colorectal cancer patients was significantly higher compared to miR-137 (18.6%). Furthermore, normal tissues, adjacent to the lesions (N-Cs), displayed no observable methylation for miRNA-137, whereas 27.2% of these N-Cs showed miRNA-342 hypermethylation. MiRNA-137 hypermethylation was significantly higher in male patients and miR-342 hypermethylation correlated with patient age. Methylation status of miRNA-137 and miRNA-342 has both diagnostic and prognostic value in CRC prediction and prevention.

摘要

结直肠癌(CRC)是全球第三大常见癌症,占所有癌症的 13%。表观遗传学在癌症的诊断和预后中的作用已得到充分证实。特别是 microRNAs 影响许多与癌症相关的过程,包括细胞凋亡、增殖、分化、细胞周期控制、迁移/侵袭和代谢。miRNA-137 和 342 分别为外显子和内含子嵌入,通过超甲基化事件作为肿瘤抑制 microRNA 发挥作用。本研究探讨了 miRNA-137 和 342 作为结直肠癌患者潜在预后标志物的水平。采用甲基化特异性(MSP)聚合酶链反应(PCR)检测 51 个息肉、8 个肿瘤和 14 个正常结肠黏膜标本中 miRNA-137 和 miRNA-342 的甲基化状态。肿瘤病变中的 miRNA-137 和 miRNA-342 甲基化状态明显高于正常相邻黏膜。令人惊讶的是,结直肠癌患者 miR-342 的甲基化频率(76.3%)明显高于 miR-137(18.6%)。此外,病变相邻的正常组织(N-Cs)中未观察到 miRNA-137 的甲基化,而这些 N-Cs 中有 27.2%显示出 miR-342 高甲基化。miRNA-137 甲基化在男性患者中明显更高,而 miR-342 甲基化与患者年龄相关。miRNA-137 和 miRNA-342 的甲基化状态在 CRC 的预测和预防中具有诊断和预后价值。

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The Origin of CIMP, At Last.CIMP 的起源,终于找到了。
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