Department of Gastroenterology, Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China.
Department of Queen Mary University, Medical College of Nanchang University, Nanchang, Jiangxi 330038, P.R. China.
Mol Med Rep. 2018 Feb;17(2):2113-2120. doi: 10.3892/mmr.2017.8145. Epub 2017 Nov 23.
As one of the most aggressive types of tumor, pancreatic cancer is a principal cause of tumor‑associated mortality. Negative associations between microRNA‑29 (miR‑29) and DNA methyltransferases (DNMT) 3a and 3b have been demonstrated to be associated with the carcinogenesis of a number of types of cancer; however, this has not been completely elucidated in pancreatic cancer. In the present study, pancreatic cancer tissues (n=15) and corresponding paracancerous tissues (n=15) were obtained and the results of reverse transcription‑quantitative polymerase chain reaction analysis indicated decreased expression of miR‑29b and enhanced mRNA expression of DNMT3b in pancreatic cancer tissues, compared with the corresponding paracancerous tissues. Increased protein expression of DNMT3b was demonstrated by western blotting and immunohistochemistry. In addition, the negative association between miR‑29b and DNMT3b was noted in pancreatic cancer tissues, and luciferase reporter assays confirmed that miR‑29b was able to directly target DNMT3b in vitro. Notably, miR‑29b overexpression was able to decrease cell viability and to promote the apoptosis by targeting DNMT3b, and the knockdown of DNMT3b exhibited consistent results in vitro and in vivo. The results of the present study suggested that miR‑29b, as a tumor suppressor, may be a novel target for the development of treatments for pancreatic cancer.
作为最具侵袭性的肿瘤之一，胰腺癌是肿瘤相关死亡的主要原因。已经证明，miR-29（miR-29）与 DNA 甲基转移酶（DNMT）3a 和 3b 之间的负相关与多种类型癌症的发生有关；然而，这在胰腺癌中尚未完全阐明。在本研究中，获得了胰腺癌组织（n=15）和相应的癌旁组织（n=15），逆转录-定量聚合酶链反应分析的结果表明，与相应的癌旁组织相比，胰腺癌组织中 miR-29b 的表达降低，DNMT3b 的 mRNA 表达增强。Western blot 和免疫组织化学显示 DNMT3b 蛋白表达增加。此外，在胰腺癌组织中还观察到 miR-29b 和 DNMT3b 之间的负相关，荧光素酶报告基因检测证实 miR-29b 能够在体外直接靶向 DNMT3b。值得注意的是，miR-29b 过表达能够通过靶向 DNMT3b 降低细胞活力并促进细胞凋亡，体外和体内的 DNMT3b 敲低也得到了一致的结果。本研究的结果表明，miR-29b 作为一种肿瘤抑制因子，可能是胰腺癌治疗开发的新靶点。
