Qu Rongfeng, Hao Shuhong, Jin Xianmei, Shi Guang, Yu Qiong, Tong Xianshuang, Guo Dongrui
Department of Hematology and Oncology, The Second Hospital of Jilin University, Changchun, Jilin 130022, China.
Department of Pediatric Oncology, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
Gene. 2018 Feb 5;642:354-361. doi: 10.1016/j.gene.2017.11.019. Epub 2017 Nov 8.
Deregulation of microRNA (miRNA) has been suggested as a critical event in colon cancer development and progression. Recent studies have suggested that miR-374b is a novel cancer-related miRNA involved in several cancer types. Thus far, very little is known about the role of miR-374b in colon cancer; therefore, the goal of this study was to investigate the potential role of miR-374b in colon cancer. Here, we showed that miR-374b expression was significantly downregulated in colon cancer tissues and cell lines. Overexpression of miR-374b inhibited the proliferation and invasion of colon cancer cells, while miR-374b suppression promoted colon cancer cell proliferation and invasion. Liver receptor homolog-1 (LRH-1) was identified as a target of miR-374b in colon cancer cells. Both the mRNA and protein expression of LRH-1 were regulated by miR-374b. In addition, an inverse correlation between LRH-1 mRNA and miR-374b expression was evidenced in colon cancer specimens. Notably, overexpression of miR-374b also downregulated the Wnt signaling in colon cancer cells. Furthermore, restoration of LRH-1 expression significantly abolished the antitumor effect of miR-374b in colon cancer cells. These findings suggest that miR-374b inhibits colon cancer cell proliferation and invasion through downregulation of LRH-1 expression. Inhibiting LRH-1 by miR-374b may represent a novel therapeutic strategy for the treatment of colon cancer.
微小RNA（miRNA）失调被认为是结肠癌发生和发展中的关键事件。最近的研究表明，miR-374b是一种涉及多种癌症类型的新型癌症相关miRNA。到目前为止，关于miR-374b在结肠癌中的作用知之甚少；因此，本研究的目的是探讨miR-374b在结肠癌中的潜在作用。在此，我们发现miR-374b在结肠癌组织和细胞系中表达显著下调。miR-374b的过表达抑制了结肠癌细胞的增殖和侵袭，而miR-374b的抑制则促进了结肠癌细胞的增殖和侵袭。肝受体同源物-1（LRH-1）被确定为结肠癌细胞中miR-374b的靶点。LRH-1的mRNA和蛋白表达均受miR-374b调控。此外，在结肠癌标本中证实了LRH-1 mRNA与miR-374b表达之间呈负相关。值得注意的是，miR-374b的过表达也下调了结肠癌细胞中的Wnt信号通路。此外，LRH-1表达的恢复显著消除了miR-374b对结肠癌细胞的抗肿瘤作用。这些发现表明，miR-374b通过下调LRH-1表达来抑制结肠癌细胞的增殖和侵袭。miR-374b抑制LRH-1可能代表一种治疗结肠癌的新策略。
