Faculty of Biology, VNU University of Science, Hanoi, Vietnam.
Department of Pathophysiology, 175 Hospital, Ho Chi Minh, Vietnam.
Mol Med Rep. 2018 Aug;18(2):2476-2484. doi: 10.3892/mmr.2018.9182. Epub 2018 Jun 18.
The three genes encoding small non‑coding microRNA (miR)34a, MIR34b and MIR34c act as tumor‑suppressor genes. Their aberrant expressions regulated by DNA methylation have been frequently found in various types of cancer. In the present study, the DNA promoter methylation profiles of the MIR34 gene family were analyzed using the methylation specific polymerase chain reaction in order to clarify their association with breast and lung cancer, non‑cancerous or normal adjacent tissues. The methylation frequency of MIR34a was significantly higher in breast cancer (49.37%) compared with normal adjacent tissues (30.38%). The methylation frequency of MIR34b/c was 59.49 and 62.03% in breast cancer and normal adjacent tissues, respectively. MIR34a methylation showed a significant concordance with that of MIR34b/c only in breast cancer tissue. MIR34a methylation was significantly associated with cancer and the invasive ductal carcinoma type of breast cancer (P=0.015 and P=0.02, respectively). Methylation frequency of MIR34a and MIR34b/c was 48.42 and 56.84% in lung cancer, and 47.22 and 51.39% in pulmonary diseases, respectively. No significant association was observed between the methylation status of MIR34a and MIR34b/c, and the clinicopathological features of lung cancer or with those of non‑cancerous pulmonary diseases. Promoter methylation of MIR34a and MIR34b/c occurs frequently and concomitantly in breast and lung cancer, as well as in pulmonary diseases tissues, but not in breast normal tissues adjacent to tumor. These results of the present study emphasize the involvement of MIR34 methylation in human diseases, including cancer. Furthermore, MIR34a methylation may be a promising marker for a subtype of breast cancer.
三个基因编码小非编码 microRNA (miR)34a、MIR34b 和 MIR34c 作为肿瘤抑制基因。它们的异常表达受 DNA 甲基化调控，在各种类型的癌症中经常发现。在本研究中，采用甲基化特异性聚合酶链反应分析了 MIR34 基因家族的 DNA 启动子甲基化谱，以阐明其与乳腺癌和肺癌、非癌或正常相邻组织的关系。与正常相邻组织（30.38%）相比，乳腺癌中 MIR34a 的甲基化频率显著升高（49.37%）。乳腺癌和正常相邻组织中 MIR34b/c 的甲基化频率分别为 59.49%和 62.03%。仅在乳腺癌组织中，MIR34a 甲基化与 MIR34b/c 的甲基化具有显著一致性。MIR34a 甲基化与癌症和浸润性导管癌型乳腺癌显著相关（P=0.015 和 P=0.02）。肺癌中 MIR34a 和 MIR34b/c 的甲基化频率分别为 48.42%和 56.84%，肺部疾病中分别为 47.22%和 51.39%。未观察到 MIR34a 和 MIR34b/c 的甲基化状态与肺癌或非癌性肺部疾病的临床病理特征之间存在显著相关性。MIR34a 和 MIR34b/c 的启动子甲基化在乳腺癌和肺癌以及肺部疾病组织中频繁发生且同时发生，但在肿瘤旁正常乳腺组织中则不发生。本研究的结果强调了 MIR34 甲基化在包括癌症在内的人类疾病中的参与。此外，MIR34a 甲基化可能是乳腺癌亚型的一个有前途的标志物。
