Li Yarui, Ren Mudan, Zhao Yan, Lu Xinlan, Wang Mengyao, Hu Junbi, Lu Guifang, He Shuixiang
Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Oncol Rep. 2017 Jun;37(6):3527-3535. doi: 10.3892/or.2017.5579. Epub 2017 Apr 19.
miR-26a is known to play an important oncosuppressive role in HCC. However, its regulatory role and relationship with other non-coding RNAs is less clear. In the present study, we report that the expression levels of miR-26a and long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) were frequently downregulated in HCC tissues compared to matched non-malignant tissues. In addition, the expression levels of miR-26a and MEG3 were negatively correlated with the tumor sizes and TNM clinical stage in HCC patients. Overexpression of miR-26a significantly reduced the capacity of proliferation, invasion and migration of HCC cells. Moreover, we demonstrated that DNA methyltransferase 3b (DNMT3B) was a direct target gene of miR-26a. Overexpression of miR-26a suppressed the expression level of DNMT3B. Inhibited expression of DNMT3B showed similar tumor suppressive effects induced by miR-26a upregulation, and resulted in the upregulation of MEG3. Furthermore, we found that the expression levels of DNMT3B were upregulated in the HCC tissues compared with non-malignant tissues, and it was inversely correlated with miR-26a and MEG3 in HCC tissues. Thus, these results provided a plausible link between the observed reduction of miR-26a and MEG3 in HCCs. Together, the present study added miR-26a/DNMT3B/MEG3 axis to the complex mechanisms of HCC development.
已知miR-26a在肝癌中发挥重要的抑癌作用。然而，其调控作用以及与其他非编码RNA的关系尚不清楚。在本研究中，我们报告称，与配对的非癌组织相比，肝癌组织中miR-26a和长链非编码RNA（lncRNA）母系表达基因3（MEG3）的表达水平经常下调。此外，miR-26a和MEG3的表达水平与肝癌患者的肿瘤大小和TNM临床分期呈负相关。miR-26a的过表达显著降低了肝癌细胞的增殖、侵袭和迁移能力。此外，我们证明DNA甲基转移酶3b（DNMT3B）是miR-26a的直接靶基因。miR-26a的过表达抑制了DNMT3B的表达水平。DNMT3B的表达受抑制表现出与miR-26a上调诱导的类似肿瘤抑制作用，并导致MEG3上调。此外，我们发现与非癌组织相比，肝癌组织中DNMT3B的表达水平上调，且在肝癌组织中它与miR-26a和MEG3呈负相关。因此，这些结果为肝癌中观察到的miR-26a和MEG3减少之间提供了一个合理的联系。总之，本研究将miR-26a/DNMT3B/MEG3轴添加到了肝癌发生的复杂机制中。
