Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, China.
Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, China.
Biomed Pharmacother. 2020 May;125:109889. doi: 10.1016/j.biopha.2020.109889. Epub 2020 Feb 6.
MicroRNA-645 (miR-645) has been implicated in numerous types of human cancers including colon cancer. However, the effects and mechanisms of action of miR-645 dysregulation on the growth and malignancy of colorectal cancer (CRC) remain unclear. In this study, we demonstrated that miR-645 knockdown significantly diminished CRC cell migration and invasion and repressed epithelial-mesenchymal transition (EMT). Conversely, miR-645 overexpression enhanced CRC cell migration, invasion, and EMT. In vivo assays confirmed that miR-645 knockdown substantially reduced CRC growth and metastasis. Regarding the mechanism, ephrin-A5 (EFNA5) was identified as a direct target gene of miR-645. MiR-645 specifically targeted the 3'-untranslated region of EFNA5 mRNA and hindered its expression. EFNA5 knockdown attenuated the effects of miR-645 knockdown on CRC cell migration and invasion. Additionally, we noted a statistically significant inverse correlation between EFNA5 mRNA and miR-645 levels in tumors from 28 patients with CRC. Hence, miR-645 acts as an oncogenic miRNA that may increase CRC cell migration, invasiveness, and metastasis by targeting EFNA5.
微小 RNA-645（miR-645）与多种人类癌症有关，包括结肠癌。然而，miR-645 失调对结直肠癌（CRC）生长和恶性的影响和作用机制尚不清楚。在这项研究中，我们证明了 miR-645 敲低显著减少了 CRC 细胞的迁移和侵袭，并抑制了上皮间质转化（EMT）。相反，miR-645 的过表达增强了 CRC 细胞的迁移、侵袭和 EMT。体内实验证实，miR-645 敲低显著降低了 CRC 的生长和转移。关于机制，ephrin-A5（EFNA5）被鉴定为 miR-645 的直接靶基因。miR-645 特异性靶向 EFNA5 mRNA 的 3'-非翻译区并抑制其表达。EFNA5 敲低减弱了 miR-645 敲低对 CRC 细胞迁移和侵袭的影响。此外，我们在 28 名 CRC 患者的肿瘤中注意到 EFNA5 mRNA 和 miR-645 水平之间存在统计学上显著的负相关。因此，miR-645 作为一种致癌 miRNA，可能通过靶向 EFNA5 增加 CRC 细胞的迁移、侵袭和转移。
