Leng Yin, Chen Zhixian, Ding Hui, Zhao Xiaoxu, Qin Li, Pan Yunlong
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, No. 601, Huangpu Avenue, Guangzhou, 510632, Guangdong, People's Republic of China.
Department of Oncology, Fuda Cancer Hospital, Jinan University, Guangzhou, 510665, People's Republic of China.
Cancer Cell Int. 2021 Jan 6;21(1):17. doi: 10.1186/s12935-020-01700-2.
Recent studies have reported the involvement of microRNA-29 (miR-29) family members in human cancers through their ability to regulate cellular functions. The present study investigated biological function of miR-29b in colorectal cancer (CRC).
CRC tissues and adjacent normal tissues were collected and the expression of ETV4 and miR-29b in the tissues were identified. The relationship between ETV4 and miR-29b or ETV4 expression and the EGFR promoter was identified using dual-luciferase reporter gene and CHIP assays. The proliferation, invasion, migration, and apoptosis of CRC HCT116 cells were assayed using MTT assay, Scratch test, Transwell assay, and flow cytometry, respectively. Also, expression of epithelial-mesenchymal transition (EMT) markers, angiogenic factors, and vasculogenic mimicry formation were evaluated using RT-qPCR and Western blot.
ETV4 was upregulated, while miR-29b expression was decreased in CRC tissues. ETV4 was identified as a target gene of miR-29b, which in turn inactivated the ERK signaling pathway by targeting ETV4 and inhibiting EGFR transcription. Transfection with miR-29b mimic, siRNA-ETV4, or ERK signaling pathway inhibitor U0126 increased expression of E-cadherin and TSP-1, and CRC cell apoptosis, yet reduced expression of ERK1/2, MMP-2, MMP-9, Vimentin, and VEGF, as well as inhibiting EMT, angiogenesis, and CRC cell migration and invasion. The EMT, angiogenesis and cancer progression induced by miR-29b inhibitor were reversed by siRNA-mediated ETV4 silencing.
miR-29b suppresses angiogenesis and EMT in CRC via the ETV4/ERK/EGFR axis.
最近的研究报道了微小RNA-29（miR-29）家族成员通过调节细胞功能参与人类癌症。本研究调查了miR-29b在结直肠癌（CRC）中的生物学功能。
收集CRC组织和相邻正常组织，鉴定组织中ETV4和miR-29b的表达。使用双荧光素酶报告基因和染色质免疫沉淀（CHIP）试验鉴定ETV4与miR-29b之间的关系或ETV4表达与表皮生长因子受体（EGFR）启动子之间的关系。分别使用MTT试验、划痕试验、Transwell试验和流式细胞术检测CRC HCT116细胞的增殖、侵袭、迁移和凋亡。此外，使用逆转录-定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹法评估上皮-间质转化（EMT）标志物、血管生成因子和血管生成拟态形成的表达。
在CRC组织中ETV4上调，而miR-29b表达降低。ETV4被鉴定为miR-29b的靶基因，miR-29b通过靶向ETV4并抑制EGFR转录来使细胞外信号调节激酶（ERK）信号通路失活。用miR-29b模拟物、小干扰RNA（siRNA）-ETV4或ERK信号通路抑制剂U0126转染可增加E-钙黏蛋白和血小板反应蛋白-1（TSP-1）的表达以及CRC细胞凋亡，但降低ERK1/2、基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）、波形蛋白和血管内皮生长因子（VEGF）的表达，并抑制EMT、血管生成以及CRC细胞迁移和侵袭。siRNA介导的ETV4沉默可逆转miR-29b抑制剂诱导的EMT、血管生成和癌症进展。
miR-29b通过ETV4/ERK/EGFR轴抑制CRC中的血管生成和EMT。
Zotero 插件
