MicroRNA-26a acts as a tumor suppressor inhibiting gallbladder cancer cell proliferation by directly targeting HMGA2
MicroRNA-26a acts as a tumor suppressor inhibiting gallbladder cancer cell proliferation by directly targeting HMGA2
复制标题
DOI：
10.3892/ijo.2014.2360
复制
发表时间：
2014-06-01
影响因子：
5.2
通讯作者：
Ma, Baojin
中科院分区：
文献类型：
--
作者：
Zhou, Huading;Guo, Weijie;Ma, Baojin
microRNA（miRNAs）是一类小的、单链的、非编码RNA分子，其在人类癌症中可作为癌基因或肿瘤抑制基因。然而，miRNA在胆囊癌（GBC）中的可能功能和作用机制尚未阐明。本研究发现miR-26 a在GBC中表达下调，且miR-26 a的表达与GBC的组织学分级相关。基于功能获得性测定，miR-26 a显著抑制GBC细胞的增殖。此外，我们证明了高迁移率族AT-钩2（HMGA 2）是miR-26 a的直接靶点。结果显示，HMGA 2 mRNA水平与miR-26 a水平呈负相关。此外，我们证实重新引入HMGA 2可以拮抗miR-26 a对GBC细胞增殖的抑制作用，并且这些作用都是通过细胞周期来实现的。总之，所有这些结果表明miR-26 a表达通过靶向HMGA 2而促进GBC增殖。miR-26 a有望成为GBC患者的预后因子和治疗靶点。
MicroRNAs (miRNAs) are a class of small, single-stranded, non-coding RNA molecules which can act as oncogenes or tumor suppressor genes in human cancer. However, the possible functions and mechanisms of miRNA action in gallbladder cancer (GBC) have not been elucidated. In the present study, it was found that miR-26a was often downregulated in GBC and the expression of miR-26a was associated with neoplasm histological grade. miR-26a significantly inhibited the proliferation of GBC cells based on the gain-of-function assays. Furthermore, we demonstrated that high mobility group AT-hook 2 (HMGA2) was a direct target of miR-26a. The results showed that HMGA2 mRNA levels and miR-26a levels were negatively correlated. In addition, we confirmed that reintroduction of HMGA2 antagonized the inhibition of miR-26a to GBC cell proliferation and all these effects were achieved through the cell cycle. Together, all these results suggest that miR-26a expression contributes to GBC proliferation by targeting HMGA2. miR-26a shows promise as a prognosis factor and therapeutic target of GBC patients.