Department of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Clinical Research Center, People's Hospital of Xuyi, Jiangsu Province, China.
J Cell Physiol. 2018 Sep;233(9):6750-6757. doi: 10.1002/jcp.26383. Epub 2018 Apr 11.
Recent studies have exhibited significant roles of lncRNAs in various tumors' development, including colon cancer. Our study focused on the biological roles of lncRNA MALAT1 in colon cancer. In our study, it was demonstrated that MALAT1 was upregulated in human colon cancer cell lines including Lovo, HCT116, SW480, and HT29 cells compared to the normal human intestinal epithelial HIEC cells. Moreover, we observed that miR-129-5p was downregulated in colon cancer cells with a significant increase of HMGB1 expression. Inhibition of MALAT1 can inhibit the proliferation of colon cancer SW480 and HCT116 cells and next, bioinformatics analysis was used to predict the target microRNA of MALAT1. miR-129-5p was identified and confirmed as a direct regulator of MALAT1 and it was shown that miR-129-5p mimics were able to restrain the progression of colon cancer cells. In addition, high motility group box protein 1 (HMGB1), was predicted as a mRNA target of miR-129-5p. Furthermore, we found that MALAT1 exerted its biological functions through regulating HMGB1 by sponging miR-129-5p in vitro. Silencing MALAT1 greatly inhibited HMGB1 expression which can be reversed by miR-129-5p inhibitors. It was indicated in our investigation that MALAT1 may serve as a competing endogenous lncRNA (ceRNA) to mediate HMGB1 by sponging miR-129-5p in colon cancer. Taken together, our results indicated that MALAT1/miR-129-5p/HMGB1 axis could be provided as an important prognostic biomarker in colon cancer development.
最近的研究表明,lncRNAs 在包括结肠癌在内的各种肿瘤的发展中具有重要作用。我们的研究集中在 lncRNA MALAT1 在结肠癌中的生物学作用。在我们的研究中,与正常的人肠道上皮细胞 HIEC 细胞相比,MALAT1 在人结肠癌细胞系中包括 Lovo、HCT116、SW480 和 HT29 细胞中上调。此外,我们观察到 miR-129-5p 在结肠癌细胞中下调,同时 HMGB1 表达显著增加。抑制 MALAT1 可以抑制结肠癌 SW480 和 HCT116 细胞的增殖,然后使用生物信息学分析预测 MALAT1 的靶 microRNA。鉴定并证实 miR-129-5p 是 MALAT1 的直接调节因子,并且表明 miR-129-5p 模拟物能够抑制结肠癌细胞的进展。此外,高迁移率族蛋白 B1(HMGB1)被预测为 miR-129-5p 的 mRNA 靶标。此外,我们发现 MALAT1 通过在体外吸附 miR-129-5p 来调节 HMGB1,从而发挥其生物学功能。沉默 MALAT1 可显著抑制 HMGB1 表达,而 miR-129-5p 抑制剂可以逆转这一作用。我们的研究表明,MALAT1 可能作为竞争内源性 lncRNA(ceRNA)通过吸附 miR-129-5p 来调节 HMGB1 在结肠癌中的作用。综上所述,我们的研究结果表明,MALAT1/miR-129-5p/HMGB1 轴可作为结肠癌发展的重要预后生物标志物。