Tianjin Life Science Research Center and Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
J Cell Biochem. 2018 Feb;119(2):2124-2134. doi: 10.1002/jcb.26374. Epub 2017 Oct 23.
MicroRNA (miRNA) dysregulation has been associated with carcinogenesis in many cancers, including human colorectal cancer (hCRC). However, the effect and mechanism of miR-377-3p on CRC remains elusive. Herein, we first found that miR-377-3p was upregulated in CRC tissues and promoted tumorigenic activity by accelerating the G -S phase transition, promoting cell proliferation and epithelial-mesenchymal transition (EMT) while repressing apoptosis in CRC cells. Glycogen synthase kinase-3β (GSK-3β) was a direct target of miR-377-3p, and upregulated by miR-377-3p. Knockdown of GSK-3β partly rescued miR-377-3p-mediated malignancy characteristics. Most importantly, we showed that miR-377-3p promoted carcinogenesis by activating NF-κB pathway. Taken together, our results first reported that miR-377-3p functions as an oncogene and promotes carcinogenesis via upregulating GSK-3β expression and activating NF-κB pathway in hCRC cells.
微小 RNA（miRNA）失调与许多癌症的发生有关，包括人类结直肠癌（hCRC）。然而，miR-377-3p 对 CRC 的作用和机制仍不清楚。在此，我们首先发现 miR-377-3p 在 CRC 组织中上调，并通过加速 G1-S 期转变、促进细胞增殖和上皮-间充质转化（EMT），同时抑制 CRC 细胞凋亡，从而促进致瘤活性。糖原合酶激酶-3β（GSK-3β）是 miR-377-3p 的直接靶标，并且被 miR-377-3p 上调。GSK-3β 的敲低部分挽救了 miR-377-3p 介导的恶性特征。最重要的是，我们表明 miR-377-3p 通过激活 NF-κB 通路促进致癌作用。总之，我们的研究结果首次报道 miR-377-3p 通过上调 GSK-3β 表达和激活 NF-κB 通路在 hCRC 细胞中发挥癌基因作用并促进致癌作用。
