MicroRNA-26a inhibits proliferation and metastasis of human hepatocellular carcinoma by regulating DNMT3B-MEG3 axis
MicroRNA-26a inhibits proliferation and metastasis of human hepatocellular carcinoma by regulating DNMT3B-MEG3 axis
复制标题
MicroRNA-26a通过调节DNMT3B-MEG3轴抑制人肝细胞癌的增殖和转移
DOI：
10.3892/or.2017.5579
复制
发表时间：
2017-06-01
期刊：
影响因子：
4.2
通讯作者：
He, Shuixiang
中科院分区：
文献类型：
--
作者：
Li, Yarui;Ren, Mudan;He, Shuixiang
已知miR-26 a在HCC中发挥重要的肿瘤抑制作用。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，我们报告了miR-26 a和长链非编码RNA（lncRNA）母源性表达基因3（MEG 3）的表达水平在HCC组织中与匹配的非恶性组织相比经常下调。此外，miR-26 a和MEG 3的表达水平与HCC患者肿瘤大小和TNM临床分期呈负相关。miR-26 a过表达可显著降低肝癌细胞的增殖、侵袭和迁移能力。此外，我们证明了DNA甲基转移酶3b（DNMT 3B）是miR-26 a的直接靶基因。过表达miR-26 a可抑制DNMT 3B的表达。DNMT 3B的表达抑制显示出与miR-26 a上调诱导的肿瘤抑制作用相似，并导致MEG 3的上调。肝癌组织中DNMT 3B的表达水平明显高于癌旁组织，且与miR-26 a和MEG 3呈负相关。因此，这些结果提供了在HCC中观察到的miR-26 a和MEG 3减少之间的合理联系。总之，本研究将miR-26 a/DNMT 3B/MEG 3轴添加到HCC发展的复杂机制中。
miR-26a is known to play an important onco-suppressive 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.