Open AccessFeedback loop in miR‐449b‐3p/ADAM17/NF‐κB promotes metastasis in nasopharyngeal carcinoma
Author(s) -
Fei Qian,
Du MingYu,
Qian LuXi,
Chen HanBo,
Chen Jie,
Zhu HongMing,
Tian XiaoKang,
Jiang Ning,
Gu JiaJia,
He Xia,
Yin Li
Publication year - 2019
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2469
Subject(s) - nasopharyngeal carcinoma , microrna , gene knockdown , cancer research , carcinogenesis , biology , luciferase , transfection , medicine , cell culture , cancer , biochemistry , gene , genetics , radiation therapy
An emerging body of evidence has promoted the understanding of the role of microRNAs (miRNAs) in tumorigenesis and progression, but the mediating function of miRNAs in nasopharyngeal carcinoma (NPC) development remains poorly elucidated. In this study, miR‐449b‐3p was downregulated in NPC specimens ( P < .001) and cells ( P < .05). Cytological and animal experiments provided evidence that miR‐449b‐3p inhibited NPC metastasis in vitro and in vivo. Disintegrin and metalloproteinase 17 (ADAM17) was revealed as a direct target of miR‐449b‐3p. Rescue experiments suggested that the downregulation of ADAM17 in the miR‐449b‐3p knockdown cells partially reversed the inhibition of cell invasion and migration. Luciferase reporter assay, chromatin immunoprecipitation assay, and Western blot analysis showed that ADAM17 could suppress the promoter activity and expression of miR‐449b‐3p by inducing NF‐κB transcriptional activity. In conclusion, our study provided new insights into the underlying mechanism of the invasion and metastasis of NPC. The novel miR‐449b‐3p/ADAM17/NF‐κB feedback loop could be a target for the clinical treatment of NPC.