Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, Xi'an 710069, China.
Institute of Preventive Genomic Medicine, School of Life Sciences, Northwest University, Xi'an 710069, China.
Int J Mol Sci. 2020 Sep 5;21(18):6499. doi: 10.3390/ijms21186499.
Metastasis is a well-known poor prognostic factor and primary cause of mortality in patients with colorectal cancer (CRC). Recently, with the progress of high through-put sequencing, aberrantly expressed non-coding RNAs (ncRNAs) were found to participate in the initiation and development of cancer. However, the mechanisms of ncRNA-mediated regulation of metastasis in CRC remain largely unknown. In this study, we systematically analyzed the expression network of microRNAs (miRNAs) and genes in CRC metastasis using bioinformatics, and discovered that the miR-581/SMAD7 axis could be a potential factor that drives CRC metastasis. A dual luciferase report assay and protein analysis confirmed the binding relationship between miR-581 and SMAD7. Further functional assays revealed that miR-581 inhibition could suppress cell proliferation and induce apoptosis in SW480 cells. Up-regulation or down-regulation of miR-581 could both affect cell invasion capacity and modulate epithelial to mesenchymal transition (EMT) via a SMAD7/TGFβ signaling pathway. In conclusion, our findings elucidated that miR-581/SMAD7 could be essential for CRC metastasis, and may serve as a potential therapeutic target for CRC patients.
转移是结直肠癌（CRC）患者预后不良的已知因素和主要致死原因。最近，随着高通量测序的进展，发现异常表达的非编码 RNA（ncRNA）参与了癌症的发生和发展。然而，ncRNA 介导的 CRC 转移调控机制在很大程度上仍然未知。在这项研究中，我们使用生物信息学系统地分析了 CRC 转移中的 microRNAs（miRNAs）和基因的表达网络，发现 miR-581/SMAD7 轴可能是驱动 CRC 转移的潜在因素。双荧光素酶报告分析和蛋白质分析证实了 miR-581 与 SMAD7 之间的结合关系。进一步的功能分析表明，miR-581 抑制可抑制 SW480 细胞的增殖并诱导细胞凋亡。miR-581 的上调或下调均可通过 SMAD7/TGFβ 信号通路影响细胞侵袭能力并调节上皮间质转化（EMT）。总之，我们的研究结果表明，miR-581/SMAD7 可能是 CRC 转移所必需的，并且可能成为 CRC 患者的潜在治疗靶点。
