Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Mol Carcinog. 2018 Oct;57(10):1421-1431. doi: 10.1002/mc.22868. Epub 2018 Jul 12.
The long non-coding RNA MALAT1 has been proved to promote the cell proliferation, drug resistance, invasion, and metastasis of colorectal cancer (CRC) in vitro and in vivo by regulating the expression of various oncogenes and their protein products. Our previous work discovered that the expression of the mRNA-decapping enzymes 1a (DCP1A) is upregulated in CRCs. However, the relationships between MALAT1 and DCP1A in the development of CRC and the underlying mechanisms are still unclear. In this study, we investigated the molecular mechanisms by which MALAT1 and DCP1A may be linked to contribute to the malignancies of CRCs. We found that DCP1A is a direct target molecule of MALAT1. Moreover, by screening the downstream genes of MALAT1, we noticed that microRNA 203(miR203), an oncogene suppressor in numerous cancers, is inversely correlated to both MALAT1 and DCP1A expressions. Following MALAT1 knockdown, we observed overexpression of miR203 accompanied with DCP1A downregulation to a level that reversed the promoted cell proliferation, invasion, and migration in vitro and in vivo, which could be restored by miR203 knockdown or DCP1A overexpression. These results proposed a new molecular mechanism of MALAT-miR203-DCP1A axis which is involved with the development and contributes to the malignancy of colorectal cancers.
长链非编码 RNA MALAT1 已被证明可通过调节各种癌基因及其蛋白产物的表达，在体内外促进结直肠癌（CRC）的细胞增殖、耐药性、侵袭和转移。我们之前的工作发现，mRNA 去帽酶 1a（DCP1A）的表达在 CRCs 中上调。然而，MALAT1 和 DCP1A 在 CRC 发展中的关系及其潜在机制仍不清楚。在这项研究中，我们研究了 MALAT1 和 DCP1A 可能相互作用的分子机制，以促进 CRC 的恶性发展。我们发现 DCP1A 是 MALAT1 的直接靶分子。此外，通过筛选 MALAT1 的下游基因，我们注意到 miR203（一种在许多癌症中作为致癌基因抑制剂的 microRNA）与 MALAT1 和 DCP1A 的表达呈负相关。在 MALAT1 敲低后，我们观察到 miR203 的过表达伴随着 DCP1A 的下调，其水平可逆转体外和体内促进的细胞增殖、侵袭和迁移，这可通过 miR203 敲低或 DCP1A 过表达来恢复。这些结果提出了 MALAT-miR203-DCP1A 轴参与结直肠癌发展并有助于其恶性发展的新分子机制。
