Laboratory Medicine Center, Affiliated Hospital of Nantong University, No.20 Xisi Road, 226001, Nantong, Jiangsu Province, China.
Department of Clinical Laboratory, The Third People's Hospital of Nantong, No.60 Middle Qingnian Road, 226006, Nantong, Jiangsu Province, China.
Cell Death Dis. 2018 Sep 24;9(10):993. doi: 10.1038/s41419-018-0969-z.
Early evidence indicates that the long non-coding RNA CCAL plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of CCAL in gastric tumourigenesis and progression remain largely unknown. We observed that CCAL was upregulated in gastric cancer tissues and was associated with the tumour-node-metastasis stage. Functional experiments showed that CCAL promoted gastric cancer cell proliferation and metastasis in vitro and in vivo. Luciferase reporter assay indicated that CCAL directly bind to miR-149. Moreover, knockdown of CCAL significantly reduced the expression of FOXM1, a direct target of miR-149. We also showed that FOXM1 suppression by miR-149 could be partially rescued by CCAL overexpression. In addition, we identified a negative correlation between the mRNA expression of CCAL and miR-149 in gastric cancer tissues. Furthermore, we observed a negative correlation between the expression of miR-149 and FOXM1 and a positive correlation between CCAL and FOXM1 levels. These results demonstrated that the CCAL/miR-149/FOXM1 axis functions as a key regulator in gastric cancer metastasis and CCAL potentially represents a biomarker for diagnosis and potential target for therapy in the future.
早期证据表明,长链非编码 RNA CCAL 在癌症进展和转移中发挥着关键作用。然而,CCAL 在胃癌发生和进展中的整体生物学作用和临床意义在很大程度上仍然未知。我们观察到 CCAL 在胃癌组织中上调,并与肿瘤-淋巴结-转移分期相关。功能实验表明,CCAL 促进了胃癌细胞在体外和体内的增殖和转移。荧光素酶报告基因实验表明,CCAL 可以直接与 miR-149 结合。此外,CCAL 的敲低显著降低了 miR-149 的直接靶标 FOXM1 的表达。我们还表明,miR-149 对 FOXM1 的抑制作用可以被 CCAL 的过表达部分挽救。此外,我们在胃癌组织中鉴定到 CCAL 和 miR-149 的 mRNA 表达之间存在负相关。此外,我们观察到 miR-149 的表达与 FOXM1 呈负相关,CCAL 与 FOXM1 水平呈正相关。这些结果表明,CCAL/miR-149/FOXM1 轴在胃癌转移中起着关键调节作用,CCAL 可能代表未来诊断的生物标志物和潜在的治疗靶点。